Bmi1 gene silencing inhibits the proliferation and invasiveness of human hepatocellular carcinoma cells and increases their sensitivity to 5-fluorouracil.
Bmi1 gene silencing inhibits the proliferation and invasiveness of human hepatocellular carcinoma cells and increases their sensitivity to 5-fluorouracil.
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DOI：
10.3892/or.2012.2189
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发表时间：
2013-03
期刊：
影响因子：
4.2
通讯作者：
Rui Zhang;Lei-bo Xu;X. Yue;Xian-Huan Yu;Jie Wang;Chao Liu
中科院分区：
文献类型：
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作者：
Rui Zhang;Lei-bo Xu;X. Yue;Xian-Huan Yu;Jie Wang;Chao Liu
据报道，Bmi 1基因在癌症的发生和发展中起重要作用。本研究的目的是探讨RNA干扰（RNAi）介导的Bmi 1基因表达沉默对肝癌细胞增殖和侵袭力的影响以及对肝癌患者化疗疗效的影响。应用Bmi 1-siRNA（small interfering RNA）沉默肝癌细胞系HepG 2和Bel-7402中的Bmi 1基因，通过实时定量逆转录-聚合酶链反应（qRT-PCR）和Western blotting检测其表达水平。采用CCK-8法、transwell法、DAPI染色法和流式细胞术分别检测Bmi 1基因沉默的肿瘤细胞的增殖、迁移能力和对5-FU的敏感性。Bmi 1-siRNA在mRNA和蛋白水平上抑制HCC细胞中Bmi 1的表达。与对照细胞相比，用Bmi 1-siRNA处理的HCC细胞的增殖和迁移显著降低。Bmi 1基因沉默可显著增加5-FU诱导的凋亡细胞比例，降低5-FU的IC 50值。通过RNAi下调Bmi 1基因可以抑制肝癌细胞的增殖和侵袭能力，并增加其对5-FU治疗的敏感性。
The Bmi1 gene has been reported to play important roles in cancer initiation and progression. The aim of this study was to investigate the effects of RNA interference (RNAi)-mediated silencing of Bmi1 gene expression on the proliferation and invasiveness of hepatocellular carcinoma (HCC) cells and on the efficacy of chemotherapy in HCC patients. The Bmi1 gene was silenced by Bmi1-siRNA (small interfering RNA) in the human HCC cell lines HepG2 and Bel-7402, and the gene expression levels were assayed by real-time quantitative reverse transcription-polymerase chain reaction (qRT-PCR) and western blotting. The proliferation and migration of Bmi1-silenced tumor cells and their sensitivity to 5-FU treatment were determined by Cell Counting Kit-8 (CCK-8), transwell assays and 4',6-diamidino-2-phenylindole (DAPI) staining and flow cytometry, respectively. Bmi1-siRNA inhibited the Bmi1 expression at both the mRNA and protein levels in HCC cells. Proliferation and migration of HCC cells treated with Bmi1-siRNA was significantly lower compared to that of the control cells. Moreover, Bmi1 gene silencing increased the percentage of apoptotic cells treated by 5-FU and decreased the IC50 values of 5-FU to a greater extent. Downregulation of the Bmi1 gene by RNAi can inhibit the proliferation and invasivesness of HCC cells and increase their sensitivity to 5-FU treatment.