丙戊酸钠协同紫杉醇对肺癌A549细胞株血管新生相关因子表达的影响

The Effects of VPA Combined with PTX on the Expression of Angiogenesis Related Factors in A549 Lung Cancer Cell Line

目的:研究组蛋白脱乙酰化酶(HDAC)抑制剂丙戊酸钠(VPA)联合紫杉醇对肺癌A549细胞血管内皮生长因子(VEGF)、Ang-2表达的影响,探讨其对肺癌细胞血管新生及对其增殖、凋亡的影响。方法:实验分为对照组、紫杉醇组、丙戊酸钠组、紫杉醇与丙戊酸钠的联合用药组,实时定量PCR及Western Blot方法分析各组A549细胞VEGF、Ang-2基因的mRNA及蛋白水平变化情况。结果:VPA组、紫杉醇组及联合用药组均可下调VEGF、Ang-2 mRNA及蛋白表达,其中联合用药组最低,差别有统计学意义。结论:HDAC抑制剂丙戊酸钠可能通过其组蛋白脱乙酰化酶的作用协同紫杉醇调节血管新生相关因子的表达,阻碍肺癌的血管新生,从而抑制肺癌细胞的生长增殖、促进其凋亡,阻碍肺癌的进展。

Objective： To investigate the effects of valproic acid,one of histone deacetylase（ HDAC） inhibitors,combinations with PTX,on the expression of vascular endothelial growth factor（ VEGF） and Ang-2of the lung cancer cell line A549 cell. Explore their significance of cell proliferation,apoptosis and metastasis on A549 cell. Methods： Set the A549 cell to four groups： control group,PTX group,VPA group and VPA combined with PTX group. Determine the mRNA and protein of VEGF and Ang-2 by quantitative PCR and Western Blot. Results： The PTX group,VPA group and VPA combined with PTX can downregulate the VEGF and Ang-2 in mRNA and protein level. The combination group of lowest level of these two genes and protein.The difference between the groups was statistically significant. Conclusion： HDAC inhibitor valproic acid may depend on its regulation of histone to inhibite cell proliferation,promote cell apoptosis of A549 cell and inhibit the angiogenesis by regulating the VEGF and Ang-2 expression.