| Zhu Lihua,Xu Gang,Gong Aihua,Wang Yan,Xue Hui,Zhang Li,Wu Chaoyang.The effects of Stattic, a STAT3 inhibitor, on the growth, migration and radiosensitivity of liver cancer cells Bel-7402[J].Chinese Journal of Radiological Medicine and Protection,2015,35(6):413-418 |
| The effects of Stattic, a STAT3 inhibitor, on the growth, migration and radiosensitivity of liver cancer cells Bel-7402 |
| Received:December 24, 2014 |
| DOI：10.3760/cma.j.issn.0254-5098.2015.06.003 |
| KeyWords:Stattic Radiosensitivity Hepatocellular carcinoma cell Cell invasion Cell apoptosis |
| FundProject:国家自然科学基金(81372718) |
| Author Name | Affiliation | E-mail | | Zhu Lihua | Department of Radiation Oncology, Zhenjiang First People's Hospital, Zhenjiang 212002, China | | | Xu Gang | Department of Radiation Oncology, Zhenjiang First People's Hospital, Zhenjiang 212002, China | | | Gong Aihua | 江苏大学医学院细胞生物学实验室 | | | Wang Yan | Department of Radiation Oncology, Zhenjiang First People's Hospital, Zhenjiang 212002, China | | | Xue Hui | Department of Radiation Oncology, Zhenjiang First People's Hospital, Zhenjiang 212002, China | | | Zhang Li | 江苏大学医学院细胞生物学实验室 | | | Wu Chaoyang | Department of Radiation Oncology, Zhenjiang First People's Hospital, Zhenjiang 212002, China | wuchaoyang9@163.com |
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| Abstract:: |
| Objective To study the effects and preliminary mechanism of Stattic (Y705), an inhibitor of the signal transducer and activator of transcription-3 (STAT3), on the growth, migration, invasion and radiosensitization of hepatocellular carcinoma cell line Bel-7402. Methods Bel-7402 cells were divided to four groups: blank control group, Stattic treatment group, radiation group, and Stattic combined with radiation group. The cell growth and proliferation were detected by using CCK8 kit. The influence of Stattic on radiation sensitivity of Bel-7402 cells was determined by clone formation assay. The cell migration and invasion ability were tested by scratch migration assay and transwell assay, respectively. The protein expressions of STAT3, p-STAT3, Bax, Bcl-2, Caspase-3, Cleaved Caspase-3, MMP-2 and MMP-9 were quantified by Western blotting assay. Results Stattic significantly inhibited the growth of human hepatocellular carcinoma Bel-7402 cells with a dose-depended manner. The IC50 of Stattic after 48 h treatment was 2.5 μmol/L. When 1.0 μmol/L Stattic was combined with 8 Gy X-rays, there was a synergistic effect in inhibition of cell proliferation with a inhibition rate of (15.00±1.87) %(F=63.30,P<0.05). Scratch migration assay and transwell invasion assay showed that the migration and invasion abilities of the combination group were significantly reduced. In addition, compared with the radiation group, the SF2, D0 and Dq values obtained from survival curve were decreased (t=4.20,6.92,9.32,P<0.05),the protein expressions of p-STAT3,MMP-2,MMP-9 were reduced(t=5.32,6.02,13.26,P<0.05), the protein expressions of Bax and Cleaved Caspase-3 were increased in the combination group(t=-7.82,-14.09,P<0.05),meanwhile the protein expressions of Bcl-2 was decreased(t=18.43,P<0.05). When the concentration of Stattic was 0.5 μmol/L, the radiation sensitization ratio at 2 Gy (SERSF2) was 1.22. Conclusions By inhibiting the activation of the p-STAT3 in Bel-7402 cells, stattic could induce cell apoptosis and increase the radiosensitivity, down regulate MMP-2 and MMP-9 and thereby reduce the invasion and migration of tumor cells. |
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