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探讨去乙酰化酶抑制剂丙戌酸钠(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。随后利用 CCK8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,Westernblotting检测 pAkt、pSmad3、aH3、aH4等的水平变化。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组中,VPA+MET组中 pAkt、pmTOR和 pSmad3蛋白水平明显降低,伴随 H3、H4乙酰化水平显著升高(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(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。
To investigate the antitumor effect of the deacetylase inhibitor sodium valproate (VPA) and metformin (MET) in prostate cancer PC-3 cells. Methods PC-3 cells were divided into control group, VPA group, MET group and VPA + MET group. Then the activity of tumor cells was detected by CCK8, the invasion and metastasis of tumor was detected by Transwell technique, and the levels of pAkt, pSmad3, aH3 and aH4 were detected by Western blotting. Results Both VPA group and MET group inhibited the invasion and metastasis of tumor cells and the activity of tumor cells. VPA + MET inhibited the invasion and metastasis of tumor cells and the activity of tumor cells more significantly than VPA group and MET group. The levels of pAkt, pmTOR and pSmad3 in VPA + MET group were significantly lower than those in control group and MET group, and the levels of acetylation of H3 and H4 were significantly increased (P <0.05). Conclusions VPA and MET combined with two drugs have more significant advantages than single drug. This advantage may be through the regulation of both TGF-β and rapamycin target protein (mTOR) pathway activity and upregulation of histone aH3, aH4 achieved.