The Experts below are selected from a list of 96 Experts worldwide ranked by ideXlab platform
Kuenfeng Chen - One of the best experts on this subject based on the ideXlab platform.
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abstract 3772 shp 1 determines the radiosensitivity of liver cancer cell and Dovitinib acts as a novel radiosensitizer in hepatocellular carcinoma via targeting shp 1 stat3 signaling
Cancer Research, 2016Co-Authors: Manhsin Hung, Chaoyuan Huang, Weitien Tai, Minghsien Tsai, Chihting Shin, Chungwai Shiau, Kuenfeng ChenAbstract:Background Hepatocellular carcinoma (HCC) is one of the most lethal human malignancies and curative therapy is not an option for most patients. There is growing interest in the potential benefit of radiotherapy (RT)-integrated therapy. This study aimed to investigate the biological impacts of a novel tumor suppressor Src homology 2 (SH2) domain-containing phosphatase 1 (SHP-1) and its downstream effecter, STAT3, in regulating the radiosensitivity of HCC cells. Furthermore, we explored the efficacy and mechanism of an investigational drug, Dovitinib, used in combination with RT. Material and methods To understand the impacts of SHP-1/STAT3 signaling affects radiosensitivity, HCC cells with ectopic expression of STAT3, SHP-1 and a catalytic mutant SHP-1 were treated with or without radiotherapy and analyzed by flow cytometry and colony formation assay. Furthermore, five HCC cell lines (PLC5, Hep3B, SK-Hep1, HA59T and Huh-7) were treated with dovitnib, RT or both. The in vitro and in vivo effects of above-mentioned treatments were analyzed. Results By sub-G1 analysis and colony formation, we found that HCC cell with ectopic expression of SHP-1 was much more sensitive to RT-induced apoptotic effects, while overexpression of STAT3 or catalytic-dead mutant SHP-1 restored RT-induced reduction of HCC cell survival. Next, we investigated the effects of Dovitinib, which showed that Dovitinib treatment resulted in SHP-1-mediated downregulation of p-STAT3 and promoted potent apoptosis of HCC cells. Ectopic expression of STAT3, or inhibition of SHP-1 diminished the effects of Dovitinib on HCC cells. Furthermore, by ectopic expression and purified recombinant proteins of various mutant forms of SHP-1, the N-SH2 domain of SHP-1 was found to be required for Dovitinib treatment. Importantly, we found that Dovitinib potentiated the in vitor and in vivo effects of RT in HCC cells through affecting the SHP-1/STAT3 signaling. Conclusions SHP-1/STAT3 signaling is critically associated with the radiosensitivity of HCC cells. A combination therapy with RT and the SHP-1 agonist, such as Dovitinib, resulted in enhanced in vitro and in vivo anti-HCC effects. Citation Format: Man-Hsin Hung, Chao-Yuan Huang, Wei-Tien Tai, Ming-Hsien Tsai, Chih-Ting Shin, Szu-Yuan Wu, Chung-Wai Shiau, Kuen-Feng Chen. SHP-1 determines the radiosensitivity of liver cancer cell and Dovitinib acts as a novel radiosensitizer in hepatocellular carcinoma via targeting SHP-1/STAT3 signaling. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 3772.
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Dovitinib acts as a novel radiosensitizer in hepatocellular carcinoma by targeting shp 1 stat3 signaling
International Journal of Radiation Oncology Biology Physics, 2016Co-Authors: Manhsin Hung, Chaoyuan Huang, Weitien Tai, Minghsien Tsai, Chungwai Shiau, Chih Ting Shih, Min Hsuan Chen, Chiung Wen Kuo, Kuenfeng ChenAbstract:Purpose Hepatocellular carcinoma (HCC) is among the most lethal human malignancies, and curative therapy is not an option for most patients. There is growing interest in the potential benefit of combining targeted therapies with radiation therapy (RT). This study aimed to characterize the efficacy and mechanism of an investigational drug, Dovitinib, used in combination with RT. Methods and Materials HCC cell lines (PLC5, Hep3B, SK-Hep1, HA59T, and Huh-7) were treated with Dovitinib, RT, or both, and apoptosis and signal transduction were analyzed. Results Dovitinib treatment resulted in Src homology region 2 (SH2) domain-containing phosphatase 1 (SHP-1)-mediated downregulation of p-STAT3 and promoted potent apoptosis of HCC cells. Ectopic expression of STAT3, or inhibition of SHP-1, diminished the effects of Dovitinib on HCC cells. By ectopic expression and purified recombinant proteins of various mutant forms of SHP-1, the N-SH2 domain of SHP-1 was found to be required for Dovitinib treatment. Overexpression of STAT3 or catalytic-dead mutant SHP-1 restored RT-induced reduction of HCC cell survival. Conversely, ectopic expression of SHP-1 or activation of SHP-1 by Dovitinib enhanced the effects of RT against HCC in vitro and in vivo. Conclusions SHP-1/STAT3 signaling is critically associated with the radiosensitivity of HCC cells. Combination therapy with RT and the SHP-1 agonist, such as Dovitinib, resulted in enhanced in vitro and in vivo anti-HCC effects.
Chaoyuan Huang - One of the best experts on this subject based on the ideXlab platform.
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abstract 3772 shp 1 determines the radiosensitivity of liver cancer cell and Dovitinib acts as a novel radiosensitizer in hepatocellular carcinoma via targeting shp 1 stat3 signaling
Cancer Research, 2016Co-Authors: Manhsin Hung, Chaoyuan Huang, Weitien Tai, Minghsien Tsai, Chihting Shin, Chungwai Shiau, Kuenfeng ChenAbstract:Background Hepatocellular carcinoma (HCC) is one of the most lethal human malignancies and curative therapy is not an option for most patients. There is growing interest in the potential benefit of radiotherapy (RT)-integrated therapy. This study aimed to investigate the biological impacts of a novel tumor suppressor Src homology 2 (SH2) domain-containing phosphatase 1 (SHP-1) and its downstream effecter, STAT3, in regulating the radiosensitivity of HCC cells. Furthermore, we explored the efficacy and mechanism of an investigational drug, Dovitinib, used in combination with RT. Material and methods To understand the impacts of SHP-1/STAT3 signaling affects radiosensitivity, HCC cells with ectopic expression of STAT3, SHP-1 and a catalytic mutant SHP-1 were treated with or without radiotherapy and analyzed by flow cytometry and colony formation assay. Furthermore, five HCC cell lines (PLC5, Hep3B, SK-Hep1, HA59T and Huh-7) were treated with dovitnib, RT or both. The in vitro and in vivo effects of above-mentioned treatments were analyzed. Results By sub-G1 analysis and colony formation, we found that HCC cell with ectopic expression of SHP-1 was much more sensitive to RT-induced apoptotic effects, while overexpression of STAT3 or catalytic-dead mutant SHP-1 restored RT-induced reduction of HCC cell survival. Next, we investigated the effects of Dovitinib, which showed that Dovitinib treatment resulted in SHP-1-mediated downregulation of p-STAT3 and promoted potent apoptosis of HCC cells. Ectopic expression of STAT3, or inhibition of SHP-1 diminished the effects of Dovitinib on HCC cells. Furthermore, by ectopic expression and purified recombinant proteins of various mutant forms of SHP-1, the N-SH2 domain of SHP-1 was found to be required for Dovitinib treatment. Importantly, we found that Dovitinib potentiated the in vitor and in vivo effects of RT in HCC cells through affecting the SHP-1/STAT3 signaling. Conclusions SHP-1/STAT3 signaling is critically associated with the radiosensitivity of HCC cells. A combination therapy with RT and the SHP-1 agonist, such as Dovitinib, resulted in enhanced in vitro and in vivo anti-HCC effects. Citation Format: Man-Hsin Hung, Chao-Yuan Huang, Wei-Tien Tai, Ming-Hsien Tsai, Chih-Ting Shin, Szu-Yuan Wu, Chung-Wai Shiau, Kuen-Feng Chen. SHP-1 determines the radiosensitivity of liver cancer cell and Dovitinib acts as a novel radiosensitizer in hepatocellular carcinoma via targeting SHP-1/STAT3 signaling. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 3772.
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Dovitinib acts as a novel radiosensitizer in hepatocellular carcinoma by targeting shp 1 stat3 signaling
International Journal of Radiation Oncology Biology Physics, 2016Co-Authors: Manhsin Hung, Chaoyuan Huang, Weitien Tai, Minghsien Tsai, Chungwai Shiau, Chih Ting Shih, Min Hsuan Chen, Chiung Wen Kuo, Kuenfeng ChenAbstract:Purpose Hepatocellular carcinoma (HCC) is among the most lethal human malignancies, and curative therapy is not an option for most patients. There is growing interest in the potential benefit of combining targeted therapies with radiation therapy (RT). This study aimed to characterize the efficacy and mechanism of an investigational drug, Dovitinib, used in combination with RT. Methods and Materials HCC cell lines (PLC5, Hep3B, SK-Hep1, HA59T, and Huh-7) were treated with Dovitinib, RT, or both, and apoptosis and signal transduction were analyzed. Results Dovitinib treatment resulted in Src homology region 2 (SH2) domain-containing phosphatase 1 (SHP-1)-mediated downregulation of p-STAT3 and promoted potent apoptosis of HCC cells. Ectopic expression of STAT3, or inhibition of SHP-1, diminished the effects of Dovitinib on HCC cells. By ectopic expression and purified recombinant proteins of various mutant forms of SHP-1, the N-SH2 domain of SHP-1 was found to be required for Dovitinib treatment. Overexpression of STAT3 or catalytic-dead mutant SHP-1 restored RT-induced reduction of HCC cell survival. Conversely, ectopic expression of SHP-1 or activation of SHP-1 by Dovitinib enhanced the effects of RT against HCC in vitro and in vivo. Conclusions SHP-1/STAT3 signaling is critically associated with the radiosensitivity of HCC cells. Combination therapy with RT and the SHP-1 agonist, such as Dovitinib, resulted in enhanced in vitro and in vivo anti-HCC effects.
Manhsin Hung - One of the best experts on this subject based on the ideXlab platform.
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abstract 3772 shp 1 determines the radiosensitivity of liver cancer cell and Dovitinib acts as a novel radiosensitizer in hepatocellular carcinoma via targeting shp 1 stat3 signaling
Cancer Research, 2016Co-Authors: Manhsin Hung, Chaoyuan Huang, Weitien Tai, Minghsien Tsai, Chihting Shin, Chungwai Shiau, Kuenfeng ChenAbstract:Background Hepatocellular carcinoma (HCC) is one of the most lethal human malignancies and curative therapy is not an option for most patients. There is growing interest in the potential benefit of radiotherapy (RT)-integrated therapy. This study aimed to investigate the biological impacts of a novel tumor suppressor Src homology 2 (SH2) domain-containing phosphatase 1 (SHP-1) and its downstream effecter, STAT3, in regulating the radiosensitivity of HCC cells. Furthermore, we explored the efficacy and mechanism of an investigational drug, Dovitinib, used in combination with RT. Material and methods To understand the impacts of SHP-1/STAT3 signaling affects radiosensitivity, HCC cells with ectopic expression of STAT3, SHP-1 and a catalytic mutant SHP-1 were treated with or without radiotherapy and analyzed by flow cytometry and colony formation assay. Furthermore, five HCC cell lines (PLC5, Hep3B, SK-Hep1, HA59T and Huh-7) were treated with dovitnib, RT or both. The in vitro and in vivo effects of above-mentioned treatments were analyzed. Results By sub-G1 analysis and colony formation, we found that HCC cell with ectopic expression of SHP-1 was much more sensitive to RT-induced apoptotic effects, while overexpression of STAT3 or catalytic-dead mutant SHP-1 restored RT-induced reduction of HCC cell survival. Next, we investigated the effects of Dovitinib, which showed that Dovitinib treatment resulted in SHP-1-mediated downregulation of p-STAT3 and promoted potent apoptosis of HCC cells. Ectopic expression of STAT3, or inhibition of SHP-1 diminished the effects of Dovitinib on HCC cells. Furthermore, by ectopic expression and purified recombinant proteins of various mutant forms of SHP-1, the N-SH2 domain of SHP-1 was found to be required for Dovitinib treatment. Importantly, we found that Dovitinib potentiated the in vitor and in vivo effects of RT in HCC cells through affecting the SHP-1/STAT3 signaling. Conclusions SHP-1/STAT3 signaling is critically associated with the radiosensitivity of HCC cells. A combination therapy with RT and the SHP-1 agonist, such as Dovitinib, resulted in enhanced in vitro and in vivo anti-HCC effects. Citation Format: Man-Hsin Hung, Chao-Yuan Huang, Wei-Tien Tai, Ming-Hsien Tsai, Chih-Ting Shin, Szu-Yuan Wu, Chung-Wai Shiau, Kuen-Feng Chen. SHP-1 determines the radiosensitivity of liver cancer cell and Dovitinib acts as a novel radiosensitizer in hepatocellular carcinoma via targeting SHP-1/STAT3 signaling. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 3772.
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Dovitinib acts as a novel radiosensitizer in hepatocellular carcinoma by targeting shp 1 stat3 signaling
International Journal of Radiation Oncology Biology Physics, 2016Co-Authors: Manhsin Hung, Chaoyuan Huang, Weitien Tai, Minghsien Tsai, Chungwai Shiau, Chih Ting Shih, Min Hsuan Chen, Chiung Wen Kuo, Kuenfeng ChenAbstract:Purpose Hepatocellular carcinoma (HCC) is among the most lethal human malignancies, and curative therapy is not an option for most patients. There is growing interest in the potential benefit of combining targeted therapies with radiation therapy (RT). This study aimed to characterize the efficacy and mechanism of an investigational drug, Dovitinib, used in combination with RT. Methods and Materials HCC cell lines (PLC5, Hep3B, SK-Hep1, HA59T, and Huh-7) were treated with Dovitinib, RT, or both, and apoptosis and signal transduction were analyzed. Results Dovitinib treatment resulted in Src homology region 2 (SH2) domain-containing phosphatase 1 (SHP-1)-mediated downregulation of p-STAT3 and promoted potent apoptosis of HCC cells. Ectopic expression of STAT3, or inhibition of SHP-1, diminished the effects of Dovitinib on HCC cells. By ectopic expression and purified recombinant proteins of various mutant forms of SHP-1, the N-SH2 domain of SHP-1 was found to be required for Dovitinib treatment. Overexpression of STAT3 or catalytic-dead mutant SHP-1 restored RT-induced reduction of HCC cell survival. Conversely, ectopic expression of SHP-1 or activation of SHP-1 by Dovitinib enhanced the effects of RT against HCC in vitro and in vivo. Conclusions SHP-1/STAT3 signaling is critically associated with the radiosensitivity of HCC cells. Combination therapy with RT and the SHP-1 agonist, such as Dovitinib, resulted in enhanced in vitro and in vivo anti-HCC effects.
Pamela M Pollock - One of the best experts on this subject based on the ideXlab platform.
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the n550k h mutations in fgfr2 confer differential resistance to pd173074 Dovitinib and ponatinib atp competitive inhibitors
Neoplasia, 2013Co-Authors: Sara A Byron, Huaibin Chen, David Loch, Michael Gartside, Farhad Dehkhoda, Steven Blais, Thomas A. Neubert, Moosa Mohammadi, Andreas Wortmann, Pamela M PollockAbstract:We sought to identify fibroblast growth factor receptor 2 (FGFR2) kinase domain mutations that confer resistance to the pan-FGFR inhibitor, Dovitinib, and explore the mechanism of action of the drug-resistant mutations. We cultured BaF3 cells overexpressing FGFR2 in high concentrations of Dovitinib and identified 14 Dovitinib-resistant mutations, including the N550K mutation observed in 25% of FGFR2mutant endometrial cancers (ECs). Structural and biochemical in vitro kinase analyses, together with BaF3 proliferation assays, showed that the resistance mutations elevate the intrinsic kinase activity of FGFR2. BaF3 lines were used to assess the ability of each mutation to confer cross-resistance to PD173074 and ponatinib. Unlike PD173074, ponatinib effectively inhibited all the Dovitinib-resistant FGFR2 mutants except the V565I gatekeeper mutation, suggesting ponatinib but not Dovitinib targets the active conformation of FGFR2 kinase. EC cell lines expressing wild-type FGFR2 were relatively resistant to all inhibitors, whereas EC cell lines expressing mutated FGFR2 showed differential sensitivity. Within the FGFR2mutant cell lines, three of seven showed marked resistance to PD173074 and relative resistance to Dovitinib and ponatinib. This suggests that alternative mechanisms distinct from kinase domain mutations are responsible for intrinsic resistance in these three EC lines. Finally, overexpression of FGFR2N550K in JHUEM-2 cells (FGFR2C383R) conferred resistance (about five-fold) to PD173074, providing independent data that FGFR2N550K can be associated with drug resistance. Biochemical in vitro kinase analyses also show that ponatinib is more effective than Dovitinib at inhibiting FGFR2N550K. We propose that tumors harboring mutationally activated FGFRs should be treated with FGFR inhibitors that specifically bind the active kinase.
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the n550k h mutations in fgfr2 confer differential resistance to pd173074 Dovitinib and ponatinib atp competitive inhibitors
Faculty of Health; Institute of Health and Biomedical Innovation, 2013Co-Authors: Sara A Byron, Huaibin Chen, David Loch, Michael Gartside, Farhad Dehkhoda, Steven Blais, Thomas A. Neubert, Moosa Mohammadi, Andreas Wortmann, Pamela M PollockAbstract:We sought to identify fibroblast growth factor receptor 2 (FGFR2) kinase domain mutations that confer resistance to the pan-FGFR inhibitor, Dovitinib, and explore the mechanism of action of the drug-resistant mutations. We cultured BaF3 cells overexpressing FGFR2 in high concentrations of Dovitinib and identified fourteen Dovitinib-resistant mutations, including the N550K mutation observed in 25% of FGFR2mutant endometrial cancers (EC). Structural and biochemical in vitro kinase analyses, together with BaF3 proliferation assays, showed that the resistance mutations elevate the intrinsic kinase activity of FGFR2. BaF3 lines were used to assess the ability of each mutation to confer cross-resistance to PD173074 and ponatinib. Unlike PD173074, ponatinib effectively inhibited all the Dovitinib-resistant FGFR2 mutants except the V565I gatekeeper mutation, suggesting ponatinib but not Dovitinib targets the active conformation of FGFR2 kinase. EC cell lines expressing wild-type FGFR2 were relatively resistant to all inhibitors. Whereas EC cell lines expressing mutated FGFR2 showed differential sensitivity. Within the FGFR2mutant cell lines, 3/7 showed marked resistance to PD173074 and relative resistance to Dovitinib and ponatinib. This suggests that alternative mechanisms distinct from kinase domain mutations are responsible for intrinsic resistance in these three EC lines. Finally, overexpression of FGFR2N550K in JHUEM-2 cells (FGFR2C383R) conferred resistance (~5 fold) to PD173074, providing independent data that FGFR2N550K can be associated with drug resistance. Biochemical in vitro kinase analyses also shows ponatinib is more effective than Dovitinib at inhibiting FGFR2N550K. We propose tumors harboring mutationally activated FGFRs should be treated with FGFR inhibitors that specifically bind the active kinase.
Chungwai Shiau - One of the best experts on this subject based on the ideXlab platform.
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abstract 3772 shp 1 determines the radiosensitivity of liver cancer cell and Dovitinib acts as a novel radiosensitizer in hepatocellular carcinoma via targeting shp 1 stat3 signaling
Cancer Research, 2016Co-Authors: Manhsin Hung, Chaoyuan Huang, Weitien Tai, Minghsien Tsai, Chihting Shin, Chungwai Shiau, Kuenfeng ChenAbstract:Background Hepatocellular carcinoma (HCC) is one of the most lethal human malignancies and curative therapy is not an option for most patients. There is growing interest in the potential benefit of radiotherapy (RT)-integrated therapy. This study aimed to investigate the biological impacts of a novel tumor suppressor Src homology 2 (SH2) domain-containing phosphatase 1 (SHP-1) and its downstream effecter, STAT3, in regulating the radiosensitivity of HCC cells. Furthermore, we explored the efficacy and mechanism of an investigational drug, Dovitinib, used in combination with RT. Material and methods To understand the impacts of SHP-1/STAT3 signaling affects radiosensitivity, HCC cells with ectopic expression of STAT3, SHP-1 and a catalytic mutant SHP-1 were treated with or without radiotherapy and analyzed by flow cytometry and colony formation assay. Furthermore, five HCC cell lines (PLC5, Hep3B, SK-Hep1, HA59T and Huh-7) were treated with dovitnib, RT or both. The in vitro and in vivo effects of above-mentioned treatments were analyzed. Results By sub-G1 analysis and colony formation, we found that HCC cell with ectopic expression of SHP-1 was much more sensitive to RT-induced apoptotic effects, while overexpression of STAT3 or catalytic-dead mutant SHP-1 restored RT-induced reduction of HCC cell survival. Next, we investigated the effects of Dovitinib, which showed that Dovitinib treatment resulted in SHP-1-mediated downregulation of p-STAT3 and promoted potent apoptosis of HCC cells. Ectopic expression of STAT3, or inhibition of SHP-1 diminished the effects of Dovitinib on HCC cells. Furthermore, by ectopic expression and purified recombinant proteins of various mutant forms of SHP-1, the N-SH2 domain of SHP-1 was found to be required for Dovitinib treatment. Importantly, we found that Dovitinib potentiated the in vitor and in vivo effects of RT in HCC cells through affecting the SHP-1/STAT3 signaling. Conclusions SHP-1/STAT3 signaling is critically associated with the radiosensitivity of HCC cells. A combination therapy with RT and the SHP-1 agonist, such as Dovitinib, resulted in enhanced in vitro and in vivo anti-HCC effects. Citation Format: Man-Hsin Hung, Chao-Yuan Huang, Wei-Tien Tai, Ming-Hsien Tsai, Chih-Ting Shin, Szu-Yuan Wu, Chung-Wai Shiau, Kuen-Feng Chen. SHP-1 determines the radiosensitivity of liver cancer cell and Dovitinib acts as a novel radiosensitizer in hepatocellular carcinoma via targeting SHP-1/STAT3 signaling. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 3772.
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Dovitinib acts as a novel radiosensitizer in hepatocellular carcinoma by targeting shp 1 stat3 signaling
International Journal of Radiation Oncology Biology Physics, 2016Co-Authors: Manhsin Hung, Chaoyuan Huang, Weitien Tai, Minghsien Tsai, Chungwai Shiau, Chih Ting Shih, Min Hsuan Chen, Chiung Wen Kuo, Kuenfeng ChenAbstract:Purpose Hepatocellular carcinoma (HCC) is among the most lethal human malignancies, and curative therapy is not an option for most patients. There is growing interest in the potential benefit of combining targeted therapies with radiation therapy (RT). This study aimed to characterize the efficacy and mechanism of an investigational drug, Dovitinib, used in combination with RT. Methods and Materials HCC cell lines (PLC5, Hep3B, SK-Hep1, HA59T, and Huh-7) were treated with Dovitinib, RT, or both, and apoptosis and signal transduction were analyzed. Results Dovitinib treatment resulted in Src homology region 2 (SH2) domain-containing phosphatase 1 (SHP-1)-mediated downregulation of p-STAT3 and promoted potent apoptosis of HCC cells. Ectopic expression of STAT3, or inhibition of SHP-1, diminished the effects of Dovitinib on HCC cells. By ectopic expression and purified recombinant proteins of various mutant forms of SHP-1, the N-SH2 domain of SHP-1 was found to be required for Dovitinib treatment. Overexpression of STAT3 or catalytic-dead mutant SHP-1 restored RT-induced reduction of HCC cell survival. Conversely, ectopic expression of SHP-1 or activation of SHP-1 by Dovitinib enhanced the effects of RT against HCC in vitro and in vivo. Conclusions SHP-1/STAT3 signaling is critically associated with the radiosensitivity of HCC cells. Combination therapy with RT and the SHP-1 agonist, such as Dovitinib, resulted in enhanced in vitro and in vivo anti-HCC effects.