The Experts below are selected from a list of 189 Experts worldwide ranked by ideXlab platform
Joyce M. Koenig - One of the best experts on this subject based on the ideXlab platform.
-
Tacrolimus: in vitro effects on myelopoiesis, apoptosis, and CD11b expression.
The Journal of heart and lung transplantation : the official publication of the International Society for Heart Transplantation, 2005Co-Authors: Joyce M. Koenig, Neil Matharoo, Joseph J Stegner, Kenneth O. SchowengerdtAbstract:Background Tacrolimus is a common component of multi-drug immunosuppressive regimens that are used for the prevention of rejection in transplant recipients. Tacrolimus therapy has been associated with anemia after transplantation, and recent clinical evidence in children suggests its association with the development of neutropenia for which an alternative etiology is not apparent. Mechanisms of suspected tacrolimus-related neutropenia have not been previously elucidated. We hypothesized that this variety of neutropenia might be due to a negative effect of tacrolimus on neutrophil production and/or survival. Methods We designed in vitro studies to determine the dose-dependent effect of tacrolimus on myeloid cell production and/or apoptosis. CD34+ cells and neutrophils isolated from umbilical cord blood of term gestations were cultured with tacrolimus (0–1,000 ng/ml). To evaluate apoptosis, cells cultured for 24 hours were stained with annexin V-fluorescein isothiocyanate (V-FITC) and 7-amino-actinomycin D (7-AAD) and analyzed by flow cytometry. For clonal analysis, CD34+ cells cultured in cytokine-enhanced semi-solid media were scored for their myeloid/erythroid mix colony forming units (CFU-Mix) and myeloid (CFU-GM) progenitor cell contents. Results Tacrolimus induced a dose-dependent enhancement of Clonogenesis and survival of CD34+ cells at clinically relevant doses. Conversely, tacrolimus had no effect on the survival of mature neutrophils or on the upregulation of CD11b in response to chemotactic stimulation. Conclusion In contrast to our initial hypothesis, we observed that tacrolimus at clinically relevant concentrations enhanced Clonogenesis of neutrophil progenitors and promoted their survival. Our in vitro studies suggest that tacrolimus alone is unlikely to be a significant factor in the neutropenia observed during immunosuppressive therapy.
-
Tacrolimus: in vitro effects on neutrophil production and apoptosis
The Journal of Heart and Lung Transplantation, 2003Co-Authors: Joyce M. Koenig, Neil Matharoo, Joseph J Stegner, Kenneth O. SchowengerdtAbstract:Purpose: Tacrolimus is a common component of multi-drug immunosuppressive regimens used for the prevention of rejection in transplant recipients. Anecdotal observations and recent evidence suggest an association between tacrolimus therapy in children and the development of neutropenia. We hypothesized that this variety of neutropenia might be related to a negative effect of tacrolimus on neutrophil (PMN) production and/or survival. Methods: We designed in vitro studies to determine the dose-dependent effects of tacrolimus on PMN production and/or apoptosis. PMN and CD34 cells isolated from umbilical cord blood of term gestations were cultured in the presence of tacrolimus (0 1000 ng/mL). To evaluate apoptosis, cells cultured for 24 h were stained with Annexin-V-FITC/ AAD and analyzed by flow cytometry. For clonal analysis, CD34 cells cultured for 10 d in cytokine-enhanced semi-solid media were scored for their myeloid/erythroid (CFU-Mix), myeloid (CFU-GM), and erythroid (BFU-E) progenitor cell contents. Results: We observed that tacrolimus induced a dose-dependent enhancement of myeloid Clonogenesis of CD34 cells that peaked at 10 ng/mL (mean SD, colonies/1000 plated cells): CFU-Mix, 14 2 (0 ng/mL) vs. 30 12 (p 0.05); CFU-GM, 61 4 (0 ng/mL) vs. 160 6 (p 0.01). Tacrolimus at these doses did not consistently decrease the survival of either CD34 cells or PMNs. Conclusions: In contrast to our initial hypothesis, we observed that tacrolimus at clinically relevant concentrations enhanced Clonogenesis of PMN progenitors and inconsistently affected cell survival. Tacrolimus is generally administered in combination with other immunosuppressive drugs after solid organ transplantation. Our data suggest that tacrolimus alone is unlikely to cause the neutropenia observed in this setting.
-
L-selectin expression enhances Clonogenesis of CD34+ cord blood progenitors.
Pediatric Research, 1999Co-Authors: Joyce M. Koenig, Senen Baron, Neal A. Benson, Albert B DeisserothAbstract:L-selectin, a surface adhesion glycoprotein expressed on leukocytes, has a well-established role in mediating inflammation and lymphocyte recirculation. Recent evidence suggests that L-selectin may also influence hematopoiesis. We observed that a greater proportion of CD34+ cells express L-selectin in cord blood compared with adult bone marrow, and we hypothesized that L-selectin expression is associated with enhanced clonogenic properties. To test this, we compared CD34+/L-selectin+ cells with CD34+/L-selectin- cells in hematopoietic clonogenic assays. From CD34+/L-selectin+ cell cultures, we observed a 3-fold increase of d 12-14 colony-forming unit-granulocyte/ macrophage and multipotent progenitor cells, and a 5-fold enhancement of primitive d 21 high proliferative potential colony-forming cells compared with the progeny of CD34+/L-selectin-cells. We conclude that CD34+ cord blood cells expressing L-selectin are enriched in their clonogenic activity compared with cell fractions lacking L-selectin expression.
Fu Jun - One of the best experts on this subject based on the ideXlab platform.
-
Quantitative Proteomic Profiling Identifies SOX8 as Novel Regulator of Drug Resistance in Gestational Trophoblastic Neoplasia.
Frontiers in oncology, 2020Co-Authors: Fu Jun, Zheng Peng, Yi Zhang, Dazun ShiAbstract:The development of drug resistance remains one of the major challenges to current chemotherapeutic regimens in gestational trophoblastic neoplasia (GTN). Further understanding on the mechanisms of drug resistance would help to develop more effective therapy to treat GTN. Herein, tandem mass tag-based (TMT) quantitative proteomic technique was used to establish drug resistance-related proteomic profiles in chemoresistant GTN cell models (JEG3/MTX, JEG3/VP16, JEG3/5-Fu). In total, we identified 5,704 protein groups, among which 4,997 proteins were quantified in JEG3 and its chemoresistant sublines. Bioinformatics analysis revealed that multiple biological processes/molecular pathways/signaling networks were involved in the regulation of drug resistance in chemoresistant JEG3 sublines. SOX8 was upregulated in all the three chemoresistant sublines, and its function was further investigated. Knockdown of SOX8 significantly reduced cell viability, impaired soft agar Clonogenesis, and increased caspase-3 activities after drug treatment in JEG3 chemoresistant sublines. In addition, over-expression of SOX8 promoted cell survival, enhanced soft agar Clonogenesis, and attenuated caspase-3 activities after drug treatment in GTN cells. Importantly, SOX8 might be a potential regulator of reactive oxygen species (ROS) homeostasis, as SOX8 regulated the expression of antioxidant enzymes (GPX1, HMOX1) and reduced drug-induced ROS accumulation in GTN cell models. Collectively, SOX8 might promote drug resistance through attenuating the accumulation of ROS induced by chemotherapeutic drugs in GTN cells. Targeting SOX8 might be useful to sensitize GTN cells to chemotherapy.
-
Quantitative proteomic analysis identifies novel regulators of methotrexate resistance in choriocarcinoma.
Gynecologic oncology, 2020Co-Authors: Fu Jun, Zheng Peng, Yi Zhang, Dazun ShiAbstract:Abstract Objective Although methotrexate (MTX) is commonly used for the treatment of choriocarcinoma, chemoresistance to MTX may occur in a considerable fraction of patients. Further understanding on the mechanisms of MTX resistance would help to develop more effective therapy for choriocarcinoma. Methods Quantitative proteomic approach involving TMT labeling and LC-MS/MS was used to identify MTX resistance-related proteomic profiles in choriocarcinoma cell models. Pathway and process enrichment analysis were conducted to identify MTX resistance-related biological processes/molecular pathways. CCK-8 viability assay, clonogenic survival assay, and BrdU incorporation analysis were used to examine the chemosensitivity to MTX in choriocarcinoma cells. Results In total, 5704 protein groups were identified, among which 4997 proteins were quantified. Bioinformatic analysis revealed that multiple biological processes/molecular pathways might be associated with MTX resistance in JEG3/JEG3/MTX cell systems. DPP4 and METTL7A were selected for further investigation. Increased expression of DPP4 or METTL7A was observed in MTX-resistant cancer cell lines and choriocarcinoma tissues. Knockdown of DPP4 or METTL7A significantly decreased cell viability, impaired Clonogenesis, and increased apoptosis after MTX treatment in JEG3/MTX and JAR/MTX cells; while over-expression of DPP4 or METTL7A promoted cell viability and reduced apoptosis following exposure to MTX in JEG3, JAR and BEWO cells. Further, DPP4 and METTL7A differentially activated prosurvival signaling pathways including PI3K/AKT, ERK1/2 and STAT3, and attenuated the accumulation of reactive oxygen species (ROS) in choriocarcinoma cell lines. Conclusions DPP4 and METTL7A might promote MTX resistance through activating pro-survival signaling pathways and attenuating the accumulation of ROS in choriocarcinoma cells. Targeting DPP4 and METTL7A might be useful to sensitize choriocarcinoma cells to MTX-based chemotherapy.
-
Overexpression of ID1 promotes tumor progression in penile squamous cell carcinoma.
Oncology reports, 2018Co-Authors: Mingfeng Chen, Yin Wang, Sailan Wen, Fu JunAbstract:Penile squamous cell carcinoma (PSCC) occurs more frequently in developing countries, and is commonly diagnosed at an advanced stage with an unfavorable prognosis. At present, few biomarkers for PSCC have been identified and used in clinical practice. Aberrant expression of inhibitor of DNA binding 1 (ID1) has been suggested as a potential regulator of tumor progression in various types cancer. Herein, we evaluated ID1 expression in PSCC and analyzed its association with the clinicopathological parameters of PSCC. Our findings indicated that ID1 overexpression is associated with histological subtype and lymph node metastasis. Kaplan‑Meier survival analysis showed that the overexpression of ID1 is associated with unfavorable cancer‑specific survival. In Cox proportional hazard models, ID1 overexpression was found to be an independent predictor of cancer‑specific survival. Furthermore, we investigated the function of ID1 in PSCC using a PSCC cell line Penl1. Silencing of ID1 expression retarded cell growth, inhibited Clonogenesis, and attenuated cell migration and invasion in Penl1 cells. ID1 may regulate key oncogenic and metastasis‑related molecules, as depletion of ID1 expression affected the levels of p‑AKT, p16, PTEN and cleaved caspase‑3, and reduced MMP2/9 secretion in Penl1 cells. Nevertheless, the mRNA expression of p16 and PTEN increased following ID1 knockdown, suggesting that ID1 may repress p16 and PTEN expression in Penl1 cells. Therefore, overexpression of ID1 could serve as a potential prognostic biomarker for the clinical management of PSCC. Strategies targeting ID1‑regulated signaling pathways may have therapeutic benefit in PSCC.
David A Frank - One of the best experts on this subject based on the ideXlab platform.
-
abstract p5 07 01 granulin a novel stat3 interacting protein promotes breast cancer tumorigenicity
Cancer Research, 2015Co-Authors: Simion Kreimer, Sarah R Walker, Andrea L Richardson, Alexander R Ivanov, David A FrankAbstract:Since the neoplastic phenotype of a cell is largely driven by its gene expression patterns, increasing attention is focused on transcription factors that regulate critical mediators of tumor formation and metastatic progression like the oncogenic transcription factor, signal transducer and activator of transcription 3 (STAT3). Whereas normal cells have transient activation of STAT3 due to tight control by negative regulators, cancer cells frequently have inappropriate constitutive activation of STAT3 which drives increased expression of genes involved in tumorigenesis. However, little is known about proteins that interact with STAT3 to modulate its function. To identify novel STAT3-interacting proteins, we performed liquid chromatography tandem mass spectrometry-based profiling of STAT3-containing complexes immunoprecipitated from the triple-negative breast cancer cell lines MDA-MB-468 and SUM159PT, which have constitutively active STAT3. We identified granulin (GRN) as a novel STAT3-interacting protein and validated the STAT3-GRN interaction in breast cancer cells by co-immunoprecipitation. To investigate the functional effect of GRN on STAT3 activity, we silenced GRN using small interfering RNA. We found that GRN was necessary for constitutive and maximal cytokine-induced STAT3 transcriptional activity in breast cancer cells. GRN modulated cytokine-induced STAT3 function by enhancing STAT3 DNA binding and increasing the time-integrated amount of STAT3 activation and nuclear translocation. Silencing GRN mirrored the effect of silencing STAT3 on reducing the viability, Clonogenesis, and migratory capacity of triple-negative breast cancer cells. Furthermore, GRN mRNA levels were significantly and positively correlated with STAT3 gene expression signatures indicative of STAT3 activation as well as with reduced overall survival in breast cancer patients. These studies used a proteomics approach to identify GRN as a novel STAT3 interacting protein that may serve as an important prognostic biomarker and potential therapeutic target in breast cancer. Citation Format: Jennifer E Yeh, Simion Kreimer, Sarah R Walker, Andrea Richardson, Alexander R Ivanov, David A Frank. Granulin, a novel STAT3-interacting protein, promotes breast cancer tumorigenicity [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr P5-07-01.
-
granulin a novel stat3 interacting protein enhances stat3 transcriptional function and correlates with poorer prognosis in breast cancer
Genes & Cancer, 2015Co-Authors: Simion Kreimer, Sarah R Walker, Megan M Emori, Hannah Krystal, Andrea L Richardson, Alexander R Ivanov, David A FrankAbstract:Since the neoplastic phenotype of a cell is largely driven by aberrant gene expression patterns, increasing attention has been focused on transcription factors that regulate critical mediators of tumorigenesis such as signal transducer and activator of transcription 3 (STAT3). As proteins that interact with STAT3 may be key in addressing how STAT3 contributes to cancer pathogenesis, we took a proteomics approach to identify novel STAT3-interacting proteins. We performed mass spectrometry-based profiling of STAT3-containing complexes from breast cancer cells that have constitutively active STAT3 and are dependent on STAT3 function for survival. We identified granulin (GRN) as a novel STAT3-interacting protein that was necessary for both constitutive and maximal leukemia inhibitory factor (LIF)induced STAT3 transcriptional activity. GRN enhanced STAT3 DNA binding and also increased the time-integrated amount of LIF-induced STAT3 activation in breast cancer cells. Furthermore, silencing GRN neutralized STAT3-mediated tumorigenic phenotypes including viability, Clonogenesis, and migratory capacity. In primary breast cancer samples, GRN mRNA levels were positively correlated with STAT3 gene expression signatures and with reduced patient survival. These studies identify GRN as a functionally important STAT3-interacting protein that may serve as an important prognostic biomarker and potential therapeutic target in breast cancer.
Dazun Shi - One of the best experts on this subject based on the ideXlab platform.
-
SLAMF1 Promotes Methotrexate Resistance via Activating Autophagy in Choriocarcinoma Cells.
Cancer management and research, 2020Co-Authors: Dazun Shi, Yu Zhang, Yan TianAbstract:Objective The acquisition of chemoresistance to methotrexate (MTX) still remains one of the major challenges for choriocarcinoma treatment. Herein, we aimed to evaluate the potential role of Signaling Lymphocytic Activation Molecule Family Member 1 (SLAMF1) as a possible regulator of chemoresistance to MTX in choriocarcinoma. Material and Methods MTX-resistant JEG3 and JAR sublines (JEG3/MTX, JAR/MTX) were used to study SLAMF1 function. CCK8 assay and soft agar assay were conducted to measure the cell viability and Clonogenesis of choriocarcinoma cells, respectively; MDC incorporation assay was conducted for the quantification of intracellular autophagy; BrdU labeling was used to assess the proliferative potential of choriocarcinoma cells; SLAMF1 protein expression was analyzed by Western blotting. Results Upregulation of SLAMF1 expression was observed in MTX-resistant JEG3/MTX and JAR/MTX sublines compared to their parental JEG3 and JAR cell lines, respectively. Knockdown of SLAMF1 markedly attenuated cell viability and soft agar Clonogenesis after incubation with MTX in JEG3/MTX and JAR/MTX cells. In contrast, constitutive expression of SLAMF1 rescued cell survival soft agar Clonogenesis in JEG3 and JAR cells treated with MTX. Moreover, autophagy is apparently activated in MTX-resistant JEG3/MTX and JAR/MTX sublines compared to their parental cell lines. Autophagy inhibitor 3-methyladenine and bafilomycin A1 enhanced MTX-induced cytotoxicity in MTX-resistant JEG3 and JAR sublines. Further, SLAMF1 might activate autophagy-related mechanism to promote resistance to MTX in choriocarcinoma cells. Depletion of SLAMF1 suppressed autophagy and induced apoptosis in MTX-treated JEG3/MTX and JAR/MTX cells. Conclusion SLAMF1 might promote MTX resistance via activating protective autophagy in choriocarcinoma cell lines. Targeting SLAMF1 might be a useful therapeutic strategy to sensitize choriocarcinoma cells to MTX-based regimens.
-
Quantitative Proteomic Profiling Identifies SOX8 as Novel Regulator of Drug Resistance in Gestational Trophoblastic Neoplasia.
Frontiers in oncology, 2020Co-Authors: Fu Jun, Zheng Peng, Yi Zhang, Dazun ShiAbstract:The development of drug resistance remains one of the major challenges to current chemotherapeutic regimens in gestational trophoblastic neoplasia (GTN). Further understanding on the mechanisms of drug resistance would help to develop more effective therapy to treat GTN. Herein, tandem mass tag-based (TMT) quantitative proteomic technique was used to establish drug resistance-related proteomic profiles in chemoresistant GTN cell models (JEG3/MTX, JEG3/VP16, JEG3/5-Fu). In total, we identified 5,704 protein groups, among which 4,997 proteins were quantified in JEG3 and its chemoresistant sublines. Bioinformatics analysis revealed that multiple biological processes/molecular pathways/signaling networks were involved in the regulation of drug resistance in chemoresistant JEG3 sublines. SOX8 was upregulated in all the three chemoresistant sublines, and its function was further investigated. Knockdown of SOX8 significantly reduced cell viability, impaired soft agar Clonogenesis, and increased caspase-3 activities after drug treatment in JEG3 chemoresistant sublines. In addition, over-expression of SOX8 promoted cell survival, enhanced soft agar Clonogenesis, and attenuated caspase-3 activities after drug treatment in GTN cells. Importantly, SOX8 might be a potential regulator of reactive oxygen species (ROS) homeostasis, as SOX8 regulated the expression of antioxidant enzymes (GPX1, HMOX1) and reduced drug-induced ROS accumulation in GTN cell models. Collectively, SOX8 might promote drug resistance through attenuating the accumulation of ROS induced by chemotherapeutic drugs in GTN cells. Targeting SOX8 might be useful to sensitize GTN cells to chemotherapy.
-
Quantitative proteomic analysis identifies novel regulators of methotrexate resistance in choriocarcinoma.
Gynecologic oncology, 2020Co-Authors: Fu Jun, Zheng Peng, Yi Zhang, Dazun ShiAbstract:Abstract Objective Although methotrexate (MTX) is commonly used for the treatment of choriocarcinoma, chemoresistance to MTX may occur in a considerable fraction of patients. Further understanding on the mechanisms of MTX resistance would help to develop more effective therapy for choriocarcinoma. Methods Quantitative proteomic approach involving TMT labeling and LC-MS/MS was used to identify MTX resistance-related proteomic profiles in choriocarcinoma cell models. Pathway and process enrichment analysis were conducted to identify MTX resistance-related biological processes/molecular pathways. CCK-8 viability assay, clonogenic survival assay, and BrdU incorporation analysis were used to examine the chemosensitivity to MTX in choriocarcinoma cells. Results In total, 5704 protein groups were identified, among which 4997 proteins were quantified. Bioinformatic analysis revealed that multiple biological processes/molecular pathways might be associated with MTX resistance in JEG3/JEG3/MTX cell systems. DPP4 and METTL7A were selected for further investigation. Increased expression of DPP4 or METTL7A was observed in MTX-resistant cancer cell lines and choriocarcinoma tissues. Knockdown of DPP4 or METTL7A significantly decreased cell viability, impaired Clonogenesis, and increased apoptosis after MTX treatment in JEG3/MTX and JAR/MTX cells; while over-expression of DPP4 or METTL7A promoted cell viability and reduced apoptosis following exposure to MTX in JEG3, JAR and BEWO cells. Further, DPP4 and METTL7A differentially activated prosurvival signaling pathways including PI3K/AKT, ERK1/2 and STAT3, and attenuated the accumulation of reactive oxygen species (ROS) in choriocarcinoma cell lines. Conclusions DPP4 and METTL7A might promote MTX resistance through activating pro-survival signaling pathways and attenuating the accumulation of ROS in choriocarcinoma cells. Targeting DPP4 and METTL7A might be useful to sensitize choriocarcinoma cells to MTX-based chemotherapy.
Aishu Ren - One of the best experts on this subject based on the ideXlab platform.
-
The effect of tubeimoside-1 on the proliferation, metastasis and apoptosis of oral squamous cell carcinoma in vitro
OncoTargets and therapy, 2018Co-Authors: Hongjuan Cui, Erhu Zhao, Jiangjun Cao, Ling Nie, Aishu RenAbstract:Background Tubeimoside-1 (TBMS1), a triterpenoid saponin extracted from traditional Chinese medicine tubeimoside, exerts a cytotoxic effect on several human cancer cell lines. However, no study has focused on whether TBMS1 works on oral squamous cell carcinoma (OSCC). Materials and methods We treated OSCC cells with TBMS1 to detect the effect and relevant molecular basis of TBMS1 for the first time. We chose two oral cancer cell lines, CAL27 and SCC15, for this study. First, the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenylte-trazolium bromide assay and cell proliferation 5'-bromo-2'-deoxyuridine assay were carried out to detect cell growth. Second, colony formation assay was performed to assess Clonogenesis capacity. Next apoptosis was analyzed by flow cytometry. Subsequently, wound healing and transwell assays were applied to explore cell migration. Finally, Western blot was further performed to examine corresponding proteins' expression change. Results Our data showed that TBMS1 significantly suppressed proliferation of OSCC cells in a dose- and time-dependent manner and it inhibited migration of OSCC cells as well. After treatment with TBMS1, OSCC cells underwent cell apoptosis. Furthermore, Western blot demonstrated that TBMS1 downregulated apoptosis-associated proteins such as PARP, p-ERK1/2, Bcl-2, caspase-3, caspase-7 and caspase-8 and upregulated cleaved PARP, cleaved caspase-3 and cleaved caspase-9. It could also reduce expression of c-Myc and MMP-7. Meanwhile, TBMS1 did not change the total ERK1/2 expression. Conclusion These results revealed that TBMS1 might be a potential chemotherapeutic drug for the management of OSCC.
-
Tigecycline exerts an antitumoral effect in oral squamous cell carcinoma
Oral diseases, 2015Co-Authors: Aishu Ren, Yu Qiu, Hongjuan CuiAbstract:Objective To explore whether antibacterial drug tigecycline could exert an antitumoral effect in oral squamous cell carcinoma (OSCC). Materials and Methods Two OSCC cell lines Tca8113 and KB were used in this study. To investigate the cytostatic effects of tigecycline in OSCC, cell growth was tested by trypan blue staining, MTT assay, and Brdu immunofluorescence staining. Then, the apoptosis proportion was measured by FITC Annexin-V and PI labeling, and cell cycle was determined by PI staining. The expression of caspase 3 (CASP3) and cell cycle regulatory protein was detected by Western blot assay. Finally, the Clonogenesis and tumorigenesis capacity were analyzed by soft agar growth and xenograft model. Results Here, we showed that tigecycline significantly inhibited cell growth and proliferation in OSCC cell lines Tca8113 and KB. It did not induce cell apoptosis but led to an increase of cells in G0/G1 phase with down-regulation of cyclin E2 (CCNE2) and cyclin-dependent kinase4 (CDK4) protein expression. We also showed that tigecycline inhibited colony formation in soft agar and reduced tumor growth in a xenograft model. Conclusion Our results suggested that tigecycline might be used as a novel candidate agent for the treatment of OSCC.
-
Inhibition of H3K9 methyltransferase G9a induces autophagy and apoptosis in oral squamous cell carcinoma.
Biochemical and biophysical research communications, 2015Co-Authors: Aishu Ren, Yu Qiu, Hongjuan CuiAbstract:Abstract Objective To explore whether inhibition of H3K9 Methyltransferase G9a could exert an antitumoral effect in oral squamous cell carcinoma (OSCC). Materials and methods First we checked G9a expression in two OSCC cell lines Tca8113 and KB. Next we used a special G9a inhibitor BIX01294 (BIX) to explore the effect of inhibition of G9a on OSCC in vitro. Cell growth was tested by typlan blue staining, MTT assay and Brdu immunofluorescence staining. Cell autophagy was examined by monodansylcadaverine (MDC) staining, LC3-II immunofluorescence staining and LC3-II western blot assay. Cell apoptosis was checked by FITC Annexin-V and PI labeling, tunnel staining and caspase 3 western blot assay. Finally, the effect of inhibition of G9a on Clonogenesis and tumorigenesis capacity of OSCC was analyzed by soft agar growth and xenograft model. Results Here we showed that G9a was expressed in both Tca8113 and KB cells. Inhibition of G9a using BIX significantly reduced cell growth and proliferation in Tca8113 and KB. Inhibition of G9a induced cell autophagy with conversion of LC3-I to LC3-II and cell apoptosis with the expression of cleaved caspase 3. We also found that inhibition of G9a reduced colony formation in soft agar and repressed tumor growth in mouse xenograph model. Conclusion Our results suggested that G9a might be a potential epigenetic target for OSCC treatment.