Zhang Yan, Hu Mei-Yu, Wu Wei-Zhong, Wang Zhi-Jun, Zhou Kang, Zha Xi-Liang, Liu Kang-Da
Experimental Center of Zhongshan Hospital, Fudan University, Shanghai, 200032, China.
J Cancer Res Clin Oncol. 2006 Nov;132(11):685-97. doi: 10.1007/s00432-006-0117-5. Epub 2006 Jun 20.
The change of cell mobility is one of the preconditions of tumor metastasis. Cell skeleton alteration and rearrangement of F-actin was closely related to cell mobility. Ezrin is a membrane-cytoskeleton organizer that can mediate the rearrangement and the function of F-actin. In this paper, we investigated the effect of ezrin on hepatocellular carcinoma cell growth and invasiveness.
Hepatocellular carcinoma cell lines such as MHCC-1, MHCC97-H, SF7721, SMMC7721, Hep3B, and HepG2 were chosen in this study. We first examined the expression and the distribution of ezrin and F-actin in these cell lines using immunofluorescence, RT-PCR, and the western blot. Next we used small interfering RNA (siRNA) to down-regulate ezrin expression in MHCC-1, MHCC97-H, SF7721, and HepG2 to investigate the role of ezrin in tumor cell growth and invasiveness.
Our preliminary results showed that the expression of ezrin and gamma-actin in MHCC-1, MHCC97-H, and SF7721 with higher metastatic potential were obviously up-regulated than those in SMMC7721, Hep3B, and HepG2 with lower potential. No different expression of beta-actin was found in the above tumor cell lines. The outcome of RNAi indicated that decreasing ezrin expression can notably inhibit the proliferation of the four hepatocellular carcinoma cell lines (p < 0.01, n = 10). The proportion of cells in G2-M phase also decreased after RNAi. The number of pseudopods decreased as well after RNAi treatment (p < 0.01, n = 5). The mobility and invasiveness of cancer cells decreased with decreasing ezrin expression tested by transwell assay (p < 0.01, n = 8).
Ezrin plays an important role in the process of hepatocellular carcinoma cell proliferation, migration, and invasiveness.
细胞迁移能力的改变是肿瘤转移的前提条件之一。细胞骨架改变及F-肌动蛋白重排与细胞迁移密切相关。埃兹蛋白是一种膜细胞骨架组织者，可介导F-肌动蛋白的重排及功能。本文研究了埃兹蛋白对肝癌细胞生长和侵袭能力的影响。
本研究选用了肝癌细胞系，如MHCC-1、MHCC97-H、SF7721、SMMC7721、Hep3B和HepG2。我们首先利用免疫荧光、RT-PCR和蛋白质印迹法检测这些细胞系中埃兹蛋白和F-肌动蛋白的表达及分布。接下来，我们使用小干扰RNA（siRNA）下调MHCC-1、MHCC97-H、SF7721和HepG2中埃兹蛋白的表达，以研究埃兹蛋白在肿瘤细胞生长和侵袭能力中的作用。
我们的初步结果显示，转移潜能较高的MHCC-1、MHCC97-H和SF7721中埃兹蛋白和γ-肌动蛋白的表达明显高于转移潜能较低的SMMC7721、Hep3B和HepG2。上述肿瘤细胞系中β-肌动蛋白的表达无差异。RNA干扰结果表明，降低埃兹蛋白表达可显著抑制四种肝癌细胞系的增殖（p < 0.01，n = 10）。RNA干扰后G2-M期细胞比例也降低。RNA干扰处理后伪足数量也减少（p < 0.01，n = 5）。通过Transwell实验检测，随着埃兹蛋白表达降低，癌细胞的迁移和侵袭能力下降（p < 0.01，n = 8）。
埃兹蛋白在肝癌细胞增殖、迁移和侵袭过程中起重要作用。
