EZH2抑制剂对宫颈癌HeLa细胞的抑制作用
Inhibitory effect of EZH2 inhibitor on cervical cancer HeLa cells

摘要：目的 探讨EZH2(enhancer of zeste homolog 2)抑制剂对宫颈癌HeLa细胞增殖与转移能力的抑制作用。方法 将EZH2抑制剂GSK343作用于体外培养的人宫颈癌HeLa细胞，用MTT及克隆形成率实验检测细胞生长和增殖的变化，细胞划痕实验测定细胞迁移能力的变化，Western blot检测上皮间质转化相关蛋白E-cadherin和N-cadherin的表达；同时以等体积GSK343溶剂DMSO为对照。 结果 MTT结果显示，GSK343对HeLa细胞的生长具有明显抑制作用，呈时间依赖性；克隆形成和细胞划痕实验显示，GSK343能显著抑制HeLa细胞的增殖及迁移能力；Western blot结果显示，GSK343处理后细胞上皮标志蛋白E-cadherin表达明显增高，间质标志蛋白N-cadherin表达明显减低。结论 EZH2抑制剂GSK343可抑制人宫颈癌HeLa细胞的增殖与迁移，其机制之一可能是通过抑制HeLa细胞上皮间质转化过程来实现的。
ABSTRACT: Objective To explore the inhibitory effect of enhancer of zeste homolog 2 (EZH2) inhibitor on the proliferation and migration of cervical cancer HeLa cells. Methods Cervical cancer HeLa cells were cultured with the conditioned-medium containing EZH2 inhibitor GSK343 or the same volume of the vehicle DMSO as control. The cell growth rate was measured by MTT assay and cloning formation assay. The cell migration ability was detected by wound scratch assay. Western blot assay was used to test the epithelial-mesenchymal transition related proteins, E-cadherin and N-cadherin. Results MTT assay results showed that GSK343 inhibited the growth of HeLa cells in a time-dependent manner. Cloning formation and wound scratch assays exhibited that GSK343 dramatically reduced both the proliferation and migration of HeLa cells. In addition, Western blot assay demonstrated that GSK343-treated cells were associated with upregulation of epithelial marker E-cadherin and downregulation of mesenchymal marker N-cadherin. Conclusion EZH2 inhibitor GSK343 can significantly restrain the proliferation and migration of cervical cancer HeLa cells, probably by inhibiting the process of epithelial-mesenchymal transition of the cells