丙戊酸钠增强二甲双胍对前列腺癌PC-3细胞的抗肿瘤作用

Valproic acid augments the anti-tumor potential of metformin in PC-3 cells

目的探讨去乙酰化酶抑制剂丙戊酸钠(VPA)与二甲双胍(MET)在前列腺癌PC-3细胞中的抗肿瘤作用。方法分别处理前列腺癌PC-3细胞,分为对照组、VPA组、MET组、VPA+MET组。随后采用CCK-8法检测肿瘤细胞的活性变化,Transwell技术检测肿瘤的侵袭转移能力,Western blotting检测pAkt、pSmad3、aH3、aH4等蛋白的水平变化。结果 VPA组与MET组均可抑制肿瘤细胞的侵袭转移能力与肿瘤细胞活性,而VPA+MET组对肿瘤细胞侵袭转移能力和肿瘤细胞活性的抑制较VPA组与MET组更加显著。相比较对照组和MET组,VPA+MET组中pAkt、pmTOR和pSmad3蛋白水平明显降低,伴随aH3、aH4乙酰化水平明显升高(P<0.05)。结论 VPA与MET两种药物联合应用较单一用药具有更显著的优势。这种优势可能是通过调节转化生长因子-β(TGF-β)与雷帕霉素靶蛋白(mTOR)两条通路活性及上调组蛋白aH3、aH4而实现。

Objective To explore the anti-tumor effect of valproic acid（ VPA） and metformin on human prostate cancer cells. Methods PC-3 cells were treated with VPA and metformin andmetformin＋VPA,and were devided into control group,VPA group,Met group and VPA＋MET group. The cell viability and invasion properties were detectedwith CCK-8 and Transwell assay,respectively. Related proteins including pAkt,pSmad3,aH3 and aH4 were detected with Western blotting. Results Both VPA and metformin could inhibit tumor cell migration and viability. Metformin＋VPA had much stronger anticancer effect than metformin and VPA alone. Compared with control group and MET group,the VPA＋MET group showed induced levels of Akt,pmTOR and pSmad3,but elevated levels of aH3 and aH4. Conclusion The metformin＋VPA combination has advantage over metformin mono-treatment in vitro. The regulation of transforming growth factor-β（ TGF-β） and mammalian target of rapamycin（ mTOR） pathways and the responsiveness of aH3 and aH4 might be involved in this process.