Department of Urology, Minhang Hospital Affiliated to Fudan University, Shanghai, China.
Eur Rev Med Pharmacol Sci. 2017 Sep;21(18):4032-4038.
Prostate cancer is a kind of malignancy with high occurrence in the male urogenital system. However, the mechanism of the occurrence, the progression, and the metastasis of prostate cancer are still unclear. Searching for the effective molecule target is of great significance to improve the curative effect on prostate cancer. Zinc finger E box binding protein-1 (ZEB1) protein is a member of the zinc finger transcription factor family that participates in the embryonic development and formation. ZEB1 was found to be involved in the occurrence and in the development of multiple cancers, while its role in prostate cancer still needs elucidation.
Normal prostate cell line PC-3M and prostate cancer cell line DU145 were cultured in vitro and transfected by ZEB1 siRNA. ZEB1 mRNA and protein expressions were detected by real-time PCR and Western blot assay. Cell proliferation was determined by using 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide (MTT) assay. Cell migration was evaluated by transwell assay. Cell apoptosis was evaluated by caspase-3 activity. The impact of ZEB1 on extracellular signal-regulated kinase 1 and 2 (ERK1/2) signaling pathway was assessed by Western blot assay.
ZEB1 expression significantly increased in DU145 cells compared with PC-3M cells (p<0.05). ZEB1 mRNA and protein obviously declined, cell proliferation inhibited, cell invasion suppressed, and Caspase-3 activity enhanced in DU145 cells after ZEB1 siRNA transfection (p<0.05). ZEB1 siRNA markedly decreased ERK1/2 phosphorylation in DU145 cells compared with control (p<0.05).
Inhibition of ZEB1 promoted prostate cancer apoptosis, restrained proliferation, and suppressed invasion through down-regulating ERK1/2 signaling pathway.
前列腺癌是一种在男性泌尿生殖系统中发病率较高的恶性肿瘤。然而，前列腺癌的发生、发展和转移的机制仍不清楚。寻找有效的分子靶标对于提高前列腺癌的疗效具有重要意义。锌指 E 盒结合蛋白 1（ZEB1）蛋白是锌指转录因子家族的成员，参与胚胎发育和形成。已经发现 ZEB1 参与了多种癌症的发生和发展，但其在前列腺癌中的作用仍需要阐明。
体外培养正常前列腺细胞系 PC-3M 和前列腺癌细胞系 DU145，并转染 ZEB1 siRNA。实时 PCR 和 Western blot 检测 ZEB1 mRNA 和蛋白表达。3-(4,5-二甲基-2-噻唑基)-2,5-二苯基-2-H-四唑溴盐（MTT）法检测细胞增殖。Transwell 检测细胞迁移。Caspase-3 活性检测细胞凋亡。Western blot 检测 ZEB1 对细胞外信号调节激酶 1 和 2（ERK1/2）信号通路的影响。
与 PC-3M 细胞相比，DU145 细胞中 ZEB1 表达明显增加（p<0.05）。转染 ZEB1 siRNA 后，DU145 细胞中 ZEB1 mRNA 和蛋白明显下调，细胞增殖受到抑制，细胞侵袭受到抑制，Caspase-3 活性增强（p<0.05）。与对照组相比，ZEB1 siRNA 明显降低了 DU145 细胞中 ERK1/2 的磷酸化（p<0.05）。
抑制 ZEB1 通过下调 ERK1/2 信号通路促进前列腺癌细胞凋亡、抑制增殖和侵袭。
