%A Gong Xiaodi, Yuan Haihua, Wang Jiongyi, Guo Yuehui, Kong Feifei, Jiang Bin %T Role of FOXM1 expression inbibition regulated by thiostrepton in the proliferation and apoptosis of lung cancer cells %0 Journal Article %D 2014 %J Journal of International Oncology %R 10.3760/cma.j.issn.1673-422X.2014.02.017 %P 135-140 %V 41 %N 2 %U {https://gjzlx.sdfmu.edu.cn/CN/abstract/article_9306.shtml} %8 2014-02-08 %X ObjectiveTo investigate the effect of thiostrepton (TST) on cell proliferation, apoptosis and the chemosensitivity of nonsmall cell cancer (NSCLC) cell lines A549 to AG1478 (EGFRTKI). MethodsNSCLC cell A549 was treated with TST, AG1478 or the combination of the two drugs. CCK8 cell viability assay was performed to determine the relative growth suppression rate of A549 cell. The expression level of forkhead transcription factors M1 (FOXM1) was studied by western blot. Caspase3 colorimetric assay was employed to evaluate the effect of TST on Caspase3 activity. A siRNA targeting FOXM1 was designed and transfected into A549 cells. RTPCR and western blot were used to examine the expressions of FOXM1 and proliferation and apoptosis related molecules. ResultsTST increased the chemosensitivity of A59 cells to AG1478, a kind of moleculartargeted agent to advanced lung cancer, which made the IC50 value reduce from (4.35±0.45) μmol/L to (0.73±0.05) μmol/L (t=11.02, P＜0.05). Besides, TST inhibited the expressions of FOXM1 and its effectors including cMyc, Cyclin B1 and Bcl2, while upregulated P21, Cleaved Caspase3 and Cleaved PARP. Meanwhile, TST improved the activity of Caspase3, which showed time and dosedependent effects. FOXM1 siRNA changes the expression of the downstream effectors such as cMyc, Cyclin B1, Bcl2, P21 and Cleaved PARP, which was similar to the effect of TST. Also, the fluorescent expression of Cleaved Caspase3 significantly increased in A549 cells. ConclusionTST can significantly inhibit proliferation and induce apoptosis by downregulating the expression of FOXM1, and then increase chemosensitivity of A549 cell to AG1478.