索拉非尼对肝癌组织和癌旁肝组织中SD F1-α表达的影响

摘要

Objective:To explore the mechanism of the increased invasive and metastatic potential of hepatocellular carcinoma induced by sorafenib ,by studying the expression of stromal‐derived factor 1‐α(SDF 1‐α) .Methods :BALB/c nude mice models of hepatocellular carcinoma in situ were established with cell line HCCLM 3 .The mice were divided into sorafenib group and control group ,with 6 mice in each group .Sorafenib was administered intragastrically [30 mg/(kg · d)] in sorafenib group from 2 weeks after model had been established ,while 0 .9% sodium chloride solution was given in the control group .Mice were killed after treating for 4 weeks .The mRNA expressions of inflammation‐related factors in hepatocellular carcinoma tissues and pericarcinoma liver tissues of the two groups were detected by RT‐PCR .The protein expression of SDF1‐α in hepatocellular carcinoma tissues and pericarcinoma liver tissues was measured by immunohistochemistry .The protein expression of SDF1‐αin pericarcinoma liver tissues was also detected by Western blotting .ELISA was performed to detect the SDF1‐αconcentration in peripheral blood .Results:The mRNA expression of murine SDF1‐αin hepatocellular carcinoma tissues and pericarcinoma liver tissues was significantly increased by sorafenib therapy .The results of immunohistochemistry and Western blotting showed that protein expression level of SDF1‐α in hepatocellular carcinoma tissues and pericarcinoma liver tissues was significantly up‐regulated by sorafenib .The results of ELISA assay showed that the concentration of murine SDF1‐αin peripheral blood was increased by sorafenib .Conclusions :The expression of SDF1‐α in hepatocellular carcinoma tissues and pericarcinoma liver tissues can be up‐regulated by sorafenib therapy .%目的：从基质细胞衍生因子1‐α（stromal‐derived factor 1‐α，SDF 1‐α）入手，研究索拉非尼致肝癌侵袭转移潜能增强的机制。方法：用HCCLM3细胞株建立BALB／c裸鼠原位肝癌模型并分为索拉非尼组和对照组，每组6只。索拉非尼组建模后2周开始给予索拉非尼灌胃，剂量为30 mg／（kg · d）；对照组建模后2周用0．9％氯化钠液灌胃；给药4周后处死裸鼠。采用RT‐PCR法检测两组裸鼠肝癌和癌旁肝组织中鼠源性炎性相关因子的mRNA表达；通过免疫组化染色检测肝癌和癌旁肝组织中SDF1‐α的表达；采用Western blotting检测癌旁肝组织中SDF1‐α的表达；采用ELISA法检测外周血中SDF1‐α的浓度。结果：索拉非尼治疗可以使肝癌组织以及癌旁肝组织中鼠源性SDF1‐α的mRNA表达增加。免疫组化及Western blotting检测发现，索拉非尼可明显上调肝癌及癌旁肝组织中SDF1‐α的蛋白表达水平。ELISA结果显示，索拉非尼可使外周血中鼠源性SDF1‐α的浓度升高。结论：索拉非尼治疗可明显上调肝癌组织和癌旁肝组织中SDF1‐α的表达。