ABT-737 Induces Bim Expression via JNK Signaling Pathway and Its Effect on the Radiation Sensitivity of HeLa Cells |
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Authors: | Huan Wang Yue-Bo Yang Hui-Min Shen Jian Gu Tian Li Xiao-Mao Li |
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Affiliation: | Gynecology Department, Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China.; Osaka University Graduate School of Medicine, Japan, |
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Abstract: | ABT-737 is a BH3 mimetic small molecule inhibitor that can effectively inhibit the activity of antiapoptotic Bcl-2 family proteins including Bcl2, Bcl-xL and Bcl-w, and further enhances the effect of apoptosis by activating the proapoptotic proteins (t-Bid, Bad, Bim). In this study, we demonstrate that ABT-737 improved the radiation sensitivity of cervical cancer HeLa cells and thereby provoked cell apoptosis. Our results show that ABT-737 inhibited HeLa cell proliferation and activated JNK and its downstream target c-Jun, which caused the up-regulation of Bim expression. Blockade of JNK/c-Jun signaling pathway resulted in significant down-regulation of ABT-737-induced Bim mRNA and protein expression level. Also, ABT-737 could evoke the Bim promoter activity, and enhance the radiation sensitivity of HeLa cells via JNK/c-Jun and Bim signaling pathway. Our data imply that combination of ABT-737 and conventional radiation therapy might represent a highly effective therapeutic approach for future treatment of cervical cancer. |
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