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

doi:10.6040/j.issn.1671-7554.0.2017.164

摘要/Abstract

摘要： 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。

关键词: 前列腺肿瘤, 丙戊酸钠, 二甲双胍, 转化生长因子-β, 雷帕霉素靶蛋白

Abstract: 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.

Key words: Prostate cancer, Valproicacid, Metformin, Transforming growth factor-β, Mammalian target of rapamycin

中图分类号:

R737.25

毛少为,卢国良,李亮,夏庆华. 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[J]. 山东大学学报 (医学版), 2018, 56(3): 48-53.

MAO Shaowei, LU Guoliang, LI Liang, XIA Qinghua. Valproic acid augments the anti-tumor potential of metformin in PC-3 cells[J]. Journal of Shandong University (Health Sciences), 2018, 56(3): 48-53.

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