State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Sichuan, China.
Cancer Biol Ther. 2011 Feb 15;11(4):401-9. doi: 10.4161/cbt.11.4.14178.
Polo-like kinase 1 (Plk1) is a key cell cycle regulator that is frequently overexpressed in human hepatocellular carcinomas. Blockade of the Plk1 pathway has been reported to be capable of inducing anti-tumor effect. Here, plasmids containing U6 promoter-driven shRNAs against human Plk1 were constructed and transfected in human hepatocellular carcinoma cell line HepG2. ShRNA targeting Plk1 almost completely reduced Plk1 expression in HepG2 hepatocellular carcinoma cells, as confirmed by RT-PCR and Western blot. As a consequence, HepG2 cells exhibited reduced proliferation and enhanced apoptosis in vitro. Most importantly, Treatment with Plk shRNA-DOTAP:Chol complex significantly suppressed the growth of HepG2 xenografts, accompanied with phenotypic changes in tumor cells, including proliferation inhibition and apoptosis induction. Our study suggested that shRNA-mediated silencing of Plk1 might be a novel therapeutic approach against human hepatocellular carcinoma by inhibiting tumor cells proliferation and inducing apoptosis.
丝氨酸/苏氨酸激酶 Plk1（Polo-like kinase 1）是一种细胞周期调控的关键蛋白，在人类肝癌中经常过表达。已有报道称，抑制 Plk1 通路能够诱导抗肿瘤作用。本研究构建了含 U6 启动子驱动的针对人 Plk1 的 shRNA 的质粒，并转染人肝癌细胞系 HepG2。shRNA 靶向 Plk1 能够几乎完全降低 HepG2 肝癌细胞中的 Plk1 表达，这一点通过 RT-PCR 和 Western blot 得到了证实。结果，HepG2 细胞的体外增殖减少，凋亡增加。最重要的是，Plk shRNA-DOTAP:Chol 复合物处理显著抑制了 HepG2 异种移植物的生长，同时伴随着肿瘤细胞表型的变化，包括增殖抑制和凋亡诱导。我们的研究表明，通过抑制肿瘤细胞增殖和诱导凋亡，shRNA 介导的 Plk1 沉默可能成为一种针对人类肝癌的新型治疗方法。
