氯化两面针碱对前列腺癌细胞PC-3增殖与凋亡的影响

目的 探讨氯化两面针碱对前列腺癌细胞PC-3增殖及凋亡的影响作用。方法 采用MTT、细胞划痕和Transwell侵袭实验评估氯化两面针碱对人前列腺癌细胞PC-3增殖与侵袭的影响;流式细胞术检测氯化两面针碱对PC-3细胞凋亡的影响;免疫印迹检测AKT/mTOR及细胞凋亡蛋白B细胞淋巴瘤基因-2相关X蛋白(Bax)和B细胞淋巴瘤基因-2(Bcl-2)的表达,应用PI3K通路抑制剂LY294002探讨抑制AKT通路对前列腺癌细胞PC-3的影响。结果 氯化两面针碱能抑制PC-3细胞的增殖与侵袭,且具有剂量依赖性(P<0.01)。氯化两面针碱可下调Bcl-2、而上调Bax的蛋白表达,Bax/Bcl-2比例明显上升(P<0.01),抑制AKT和mTOR通路的磷酸化,诱导前列腺癌细胞PC-3凋亡。联合应用LY294002发现,抑制AKT通路可增强氯化两面针碱对前列腺癌细胞PC-3增殖和侵袭的抑制作用。结论 氯化两面针碱能够抑制前列腺癌细胞PC-3的增殖与侵袭,诱导其凋亡,并通过抑制AKT/mTOR磷酸化发挥其抗前列腺癌作用,可作为一种潜在治疗前列腺癌的药物。

Effects of nitidine chloride on the proliferation and apoptosis of prostate cancer PC-3 cells

Objective To evaluate the effects of nitidine chloride on the proliferation and apoptosis of prostate cancer cells PC-3 in vitro. Methods MTT, scratch migration and Transwell were used to examine the changes in the proliferation and invasions of human prostate cancer cell PC-3 after nitidine chloride treatment. Flow cytometry was used to examine the changes in cell apoptosis of PC-3. Immunoblot analysis was adopted to detect the expression of AKT/mTOR, Bcell-associated x protein (Bax) and Bcell lymphoma-2 (Bcl-2). A specific PI3K inhibitor, LY294002, was used to evaluate the influence of prostate cancer cells by inhibiting AKT pathway. Results Nitidine chloride inhibited the proliferation and invasion of PC-3 cells in a dose-dependent manner (P<0.01). Nitidine chloride inhibited AKT and mTOR pathways phosphorylation, accompanied by up-regulation of Bax, and down-regulation of Bcl-2. Nitidine chloride significantly increased the ratio of Bax/Bcl-2 (P<0.01), to induce prostate cancer cells apoptosis. Furthermore, combined use of LY294002 inhibited AKT pathway, which could enhance the anti-proliferation and anti-invasion effectsof nitidine chloride. Conclusion Nitidine chloride can suppress the proliferation, migration, invasion and induce the apoptosis of prostate cancer cells in vitro. Nitidine chloride also plays a role in anti-cancer via inhibiting AKT/mTOR pathway phosphorylation, which implies that nitidine chloride may be a promising therapeutic drug for prostate cancer.