目的:从基质细胞衍生因子1-α(stromal-derived factor 1-α,SDF1-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。
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(SDF1-α).Methods:BALB/c nude mice models of hepatocellular carcinoma in situ were established with cell line HCCLM3.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 from2 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-αin 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-αin 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-αin hepatocellular carcinoma tissues and pericarcinoma liver tissues can be up-regulated by sorafenib therapy.