Or Yvonne Y Y, Chow Ariel K M, Ng Lui, Fan Sheung Tat, Yau Thomas C C, Poon Ronnie T P, Pang Roberta W C
Department of Surgery, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, SAR, P.R. China.
Mol Med Rep. 2014 Oct;10(4):2025-30. doi: 10.3892/mmr.2014.2413. Epub 2014 Jul 22.
Survivin is a member of the inhibitor of apoptosis family, which has been suggested to be crucial in the control of cell division and inhibition of apoptosis. Expression of this protein has been observed in transformed cell lines and human tumor tissues, including those from colorectal cancer, but not in terminally differentiated adult tissues. Survivin mRNA expression has frequently been detected in hepatocellular carcinoma (HCC) and its protein expression has been demonstrated to be highly correlated with proliferation index rather than apoptotic index. The present study aimed to analyze the effect of survivin on the tumorigenicity and chemosensitivity of HCC via the establishment of an HCC cell line (PLC/PRF/5) with the stable knockdown of the survivin gene (PLC‑k3). This cell line displayed significantly lower rates of survival and proliferation in assays of cell viability and proliferation, respectively, compared with those of the control cell line (PLC‑v). In addition, PLC‑k3 cells were more sensitive to cisplatin treatment, resulting in S phase arrest. These findings were further confirmed by an in vivo experiment. The data of the present study suggest that survivin is critical in promoting cell proliferation but not in inhibition of apoptosis, and enhances the chemosensitivity of HCC. Thus, the suppression of survivin expression in combination with cisplatin may contribute to the development of more effective treatments for HCC.
生存素是凋亡抑制蛋白家族的成员之一,据推测其在控制细胞分裂和抑制细胞凋亡方面起着关键作用。已在转化细胞系和人类肿瘤组织(包括来自结直肠癌的肿瘤组织)中观察到该蛋白的表达,但在终末分化的成人组织中未观察到。生存素mRNA表达在肝细胞癌(HCC)中经常被检测到,并且其蛋白表达已被证明与增殖指数高度相关,而非凋亡指数。本研究旨在通过建立生存素基因稳定敲低的HCC细胞系(PLC/PRF/5)(PLC-k3)来分析生存素对HCC致瘤性和化学敏感性的影响。与对照细胞系(PLC-v)相比,该细胞系在细胞活力和增殖测定中分别显示出显著更低的存活率和增殖率。此外,PLC-k3细胞对顺铂治疗更敏感,导致S期阻滞。这些发现通过体内实验得到进一步证实。本研究数据表明,生存素在促进细胞增殖而非抑制细胞凋亡方面起关键作用,并增强了HCC的化学敏感性。因此,抑制生存素表达联合顺铂可能有助于开发更有效的HCC治疗方法。