Role of JNK-mediated Bim Expression in ABT737 -induced Apoptosis in HeLa Cells[J]. Journal of Sun Yat-sen University (Medical Sciences), 2013, 34(5).DOI:
【Objective】 ABT-737 is a BH3 mimetic small molecule inhibitor that can effectively inhibit the activity of antiapoptotic Bcl-2 family proteins including Bcl-2
Bcl-xL and Bcl-w
and further enhances the effect of apoptosis. We explored the pivotal role of JNK-mediated Bim expression in ABT737 -induced apoptosis in HeLa cells. 【Methods】 Annexin V-PI staining was used to assess the apoptosis. The expression of JNK
phospho-JNK
c-Jun
phospho-c-Jun
Bim were detected using Western blot analysis. RT-PCR was used to detect the mRNA level of Bim. JNK specific inhibitor SP600125 or siRNA against JNK c-Jun were used to block activation of JNK. 【Results】 ABT737 significantly inhibited cell growth of HeLa cells with IC50 value of 15.7 μmol/L. ABT737 induced apoptosis in HeLa cells. JNK was activated in cells exposed to ABT737 and the phosphorylation of c-Jun also increased. In the meantime
the expression of Bim was up-regulated in HeLa cells. The up-regulation of Bim expression and apoptosis induced by ABT737 were blocked by SP600125 or small interfering RNA directed against JNK or c-Jun. 【Conclusion】 JNK/c-Jun pathway mediates Bim up-regulation in apoptosis induced by ABT737.