AMD3100下调CA9与CXCR4表达逆转索拉菲尼耐药  

AMD3100 reverses Sorafenib resistance bydown-regulating CA9 and CXCR4 expression

作　　者：秦骥伟 郑浩 徐治军 栗雪峰 孙成[1] Qin Jiwei;Zheng Hao;Xu Zhijun;Li Xuefeng;Sun Cheng(Organ Transplantation Center,The First Affiliated Hospital of University of Science and Technology of China,Hefei 230001)

机构地区：[1]中国科学技术大学附属第一医院器官移植中心,合肥230001

出　　处：《安徽医科大学学报》2023年第6期919-924,共6页Acta Universitatis Medicinalis Anhui

基　　金：安徽省自然科学基金(编号:2008085J35)。

摘　　要：目的 研究AMD3100通过调控碳酸酐酶Ⅸ(CA9)和趋化因子受体4(CXCR4)逆转人肝癌细胞对索拉菲尼的耐药性机制。方法 以人肝癌细胞Huh7和HepG2为研究对象,建立索拉菲尼耐药株Huh7/Sor和HepG2/Sor;检测索拉菲尼单独或联合使用AMD3100对Huh7、HepG2、Huh7/Sor、HepG2/Sor细胞增殖的影响;观察索拉菲尼耐药细胞与非耐药细胞侵袭能力的区别,AMD3100对肝癌细胞侵袭能力的影响;索拉菲尼单独或联合使用AMD3100对Huh7、HepG2、Huh7/Sor和HepG2/Sor细胞的CA9和CXCR4蛋白表达的调控作用。结果与对照组比较,AMD3100 (50μmol/L)可提高索拉菲尼对Huh7/Sor和HepG2/Sor细胞的增殖抑制作用(P <0.05);与Huh7细胞比较,索拉菲尼耐药株Huh7/Sor细胞的侵袭能力增强(P <0.05),AMD3100(50μmol/L)可降低Huh7和Huh7/Sor细胞的侵袭能力(P <0.05);与Huh7和HepG2细胞比较,Huh7/Sor和HepG2/Sor细胞的CA9和CXCR4蛋白表达增加(P <0.05),AMD3100(50μmol/L)可下调Huh7、HepG2、Huh7/Sor和HepG2/Sor细胞的CA9和CXCR4蛋白表达(P <0.05)。结论AMD3100可能通过下调CA9、CXCR4表达降低人肝癌细胞对索拉菲尼耐药性,增强索拉菲尼对人肝癌细胞的增殖和侵袭抑制。Objective To investigate the mechanism of AMD3100 reversing the resistance of human hepatocellular carcinoma cells to Sorafenib by regulating carbonic anhydrase Ⅸ(CA9)and chemokine receptor 4(CXCR 4).Methods The Sorafenib resistant cell lines Huh7/Sor and HepG2/Sor were established from human hepatocellular carcinoma cells Huh7 and HepG2.The effects of Sorafenib alone or in combination with AMD3100 on the proliferation of Huh7,HepG2,Huh7/Sor,HepG2/Sor cells were detected.The difference of invasive ability between Sorafenib resistant cells and non-resistant cells,and the effect of AMD3100 on the invasive ability of hepatocellular carcinoma cells were observed.And the regulation effect of Sorafenib alone or in combination with AMD3100 on the expression of CA9 and CXCR4 proteins in Huh7,HepG2,Huh7/Sor and HepG2/Sor cells was detected.Results Compared with the Control group,AMD3100(50μmol/L)increased the inhibitory effect of Sorafenib on the proliferation of Huh7/Sor and HepG2/Sor cells(P<0.05).Compared with Huh7 cells,the invasive ability of Sorafenib resistant Huh7/Sor cells was significantly enhanced(P<0.05),and AMD 3100(50μmol/L)decreased the invasive ability of Huh7 and Huh7/Sor cells(P<0.05).Compared with Huh7 and HepG2 cells,the protein expression of CA9 and CXCR4 in Huh7/Sor and HepG2/Sor cells increased(P<0.05).AMD3100(50μmol/L)down-regulated the protein expression of CA9 and CXCR4 in Huh7,HepG2,Huh7/Sor and HepG2/Sor cells(P<0.05).Conclusion AMD3100 can reduce the resistance of human hepatocellular carcinoma cells to Sorafenib by down-regulating the expression of CA9 and CXCR4,and enhance the inhibition of Sorafenib on the proliferation and invasion of human hepatocellular carcinoma cells.

关 键 词：肝细胞癌 AMD3100 碳酸酐酶Ⅸ 趋化因子受体4 索拉菲尼 耐药 

分 类 号：R735.7[医药卫生—肿瘤]