Non-toxic dose chidamide synergistically enhances platinum-induced DNA damage responses and apoptosis in Non-Small-Cell lung cancer cells

详细信息    查看全文

• 作者：You Zhou^a ; ^b ; De-Si Pan^b ; Song Shan^b ; Jing-Zhong Zhu^b ; Kun Zhang^b ; Xu-Peng Yue^b ; Li-Ping Nie^c ; Jun Wan^a ; Xian-Ping Lu^b ; Wei Zhang^a ; ¹ ; ^{zhangweispace@yeah.net" class="auth_mail} ; Zhi-Qiang Ning^b ; ² ; ^{zqning@chipscreen.com" class="auth_mail}
• 关键词：HDAC inhibitor ; Carboplatin ; Cisplatin ; Oxaliplatin ; DNA damage ; Non-small-cell lung cancer
• 刊名：Biomedicine and Pharmacotherapy
• 出版年：May 2014
• 年：2014
• 卷：68
• 期：4
• 页码：483-491
• 全文大小：2412 K

文摘

Combination of low doses of histone deacetylases inhibitors and chemotherapy drugs is considered as one of the most promising strategies to increase the anticancer efficacy. Chidamide is a novel benzamide chemical class of HDAC inhibitor that selectively inhibited HDAC1, 2, 3 and 10. We sought to determine whether chidamide may enhance platinum-induced cytotoxicity in NSCLC cells. In this study, the combination of chidamide with carboplatin showed a good synergism on growth inhibition with the mean combination index value as 0.712 and 0.639 in A549 and NCI-H157 cells, respectively. The used concentration of chidamide was non-toxic on cells by itself as low as 0.3 渭M. All of our experiments were comparisons between combination regimen and single carboplatin regimen in A549 and NCI-H157 cell lines. Phosphorylated histone H2A.X (纬H2A.X), a hall marker of DNA damage response, was dramatically increased by the combination treatment. Cell cycle analysis by flow cytometry and phosphorylation level analysis of histone H3 (Ser10) by western blotting showed that combination treatment significantly increased the percentage of G2/M phase of cells. Mitochondrial membrane potential and cleaved-PARP1 level analysis indicate that chidamide synergistically enhances carboplatin-induced apoptosis. Additionally, synergistic effects of chidamide were found when it was combined with two other platinum drugs (cisplatin and oxaliplatin). The results suggest that Chidamide in combination with platinum drugs may be a novel therapeutic option for NSCLC.