索拉非尼对MHCC97-H 肝癌细胞增殖、 侵袭以及PRL-3 蛋白表达的影响研究

Sorafenib inhibits proliferation, invasion and PRL-3 protein expression in MHCC97-H hepatocellular carcinoma cells

摘要:

目的 探讨索拉非尼对体外培养MHCC97-H 肝癌细胞中肝再生磷酸酶3（PRL-3）表达水 平的影响，以及对肝癌细胞侵袭力的作用。方法 在24、48 及72 h 测定经不同浓度梯度索拉非尼处理 MHCC97-H 肝癌细胞增殖抑制率以筛选合适的干预浓度和时间。采用MHCC97-H 肝癌细胞培养传代， 用索拉非尼干预处理，瑞氏吉姆萨法染色观察形态学变化，MTT 法检测其增殖抑制率，Western blot 法检测 PRL-3 蛋白表达水平，Transwell 实验检测癌细胞侵袭力。结果 该实验索拉非尼体外最佳干预实验浓度和时 间分别为16 μmol/L 和48 h ；索拉非尼能诱导肝癌细胞株MHCC97-H 的凋亡，肝癌细胞增殖抑制率与时间 和剂量呈正相关。经索拉非尼作用后PRL-3 蛋白也出现不同程度下降，肝癌细胞侵袭能力明显下降。结论 索拉非尼能降低MHCC97-H 肝癌细胞株中PRL-3 蛋白表达水平，降低肿瘤细胞侵袭力，从而诱导肝癌细胞 凋亡；索拉非尼降低癌细胞的侵袭可能是通过下调PRL-3 蛋白进行。

Abstract:

Objective To investigate the effect of Sorafenib on the proliferation and apoptosis of MHCC97-H human hepatocellular carcinoma cells in vitro, as well as its effect on expression of PRL-3 protein and cell invasiveness. Methods Different concentrations of Sorafenib were applied to MHCC97-H human hepatocellular carcinoma cells, and MTT assay was used to observe the inhibitory effect of Sorafenib on the cell proliferation at 24, 48 and 72 h to screen the optimum concentration of Sorafenib and intervention time. Giemsa staining was used to observe the morphological changes of the cells. Western blot was used to detect the protein expression of PRL- 3. Transwell assay was used to detect the invasiveness of the tumor cells. Results The optimum concentration and time of Sorafenib intervention were 16 μmol/L and 48 h, respectively. Sorafenib induced apoptosis of MHCC97-H hepatocellular carcinoma cells. The inhibition rate of MHCC97-H cell proliferation was positively correlated with time and dosage. Sorafenib also decreased PRL-3 protein expression to different extent. After the expression of PRL- 3 decreased, the hepatocellular carcinoma cell invasion ability was significantly inhibited. Conclusions Sorafenib can reduce the expression level of PRL-3 protein in MHCC97-H hepatocellular carcinoma cell line, and decrease the invasiveness of the cells, so as to induce the apoptosis of hepatocellular carcinoma cells. Its inhibition of cancer cell migration may be mediated by down-regulation of PRL-3 protein.