靶向阻断STAT3增强肝癌细胞H22对化疗药物阿霉素的敏感性  

Targeted blocking STAT3 enhances sensitivity of liver cancer cell H22 to chemotherapy drug doxorubicin

作　　者：王亚群[1] 韩秋菊[1] 庞敏[1] 张建[1] 

机构地区：[1]山东大学药学院免疫药理与免疫治疗学研究所,济南250012

出　　处：《中国免疫学杂志》2015年第10期1304-1309,1314,共7页Chinese Journal of Immunology

基　　金：国家自然科学基金(81373222)资助项目

摘　　要：目的:探讨STAT3阻断剂Decoy ODN与临床常用肝癌化疗药阿霉素(Doxorubicin)、5-氟尿嘧啶(5-Fu)和顺铂(cisplatin)联合使用对肝癌的治疗效果及其对免疫系统的影响。方法:肝癌细胞转染Decoy ODN后用化疗药处理,以MTT法检测肝癌细胞的增殖能力,Annexin-V/7AAD双染法检测细胞凋亡率;对H22荷瘤小鼠进行Decoy ODN和阿霉素联合治疗,观察小鼠肿瘤生长情况以及生存期;流式细胞术检测治疗后小鼠PBMC的细胞分群和活化水平,以及阿霉素或阿霉素处理的肿瘤细胞对小鼠脾脏淋巴细胞体外活化作用。结果:转染Decoy ODN以后,阿霉素对H22细胞的抑制作用显著增强,H22细胞凋亡率也明显升高。Decoy ODN和阿霉素联合治疗可明显降低小鼠肿瘤生长速度并延长荷瘤小鼠的生存期;低剂量阿霉素增加了PBMC中T细胞的比例和CD69分子的表达,以及NK细胞CD107a和IFN-γ的表达;阿霉素处理的H22细胞可促进T细胞比例的升高。结论:Decoy ODN阻断肝癌细胞STAT3后可以增强肝癌细胞H22对阿霉素的敏感性,提高化疗效果,降低化疗毒副作用,改善机体免疫功能。Objective：To investigate the theraputic effect of STAT3 Decoy-ODN combined with chemotherapy drugs for HCC commonly used in clinical,include doxorubicin （DOX）,5-fluorouracil （5-Fu） and cisplatin;and,analyzing the impact of combination therapy on the immune system.Methods：MTT assay was used to detect cell proliferation,and Annexin-V /7AAD double staining assay was used to detect the apoptosis of Decoy ODN transfected-hepatoma cells treated with chemotherapy drugs.The tumor growth and survival rate of H22 tumor-bearing mice treated with DOX combined with STAT3 Decoy-ODN or not were observed.FACS was applied to analyze the subpopulation and activation of PBMCs from tumor-bearing mice treated as above,and to evaluate the influence of DOX or DOX-treated tumor cells on spleen lymphocyte activation.Results： DOX-induced the suppression and the apoptosis of H22 were significantly increased by Decoy ODN transfection.The combination treatment of Decoy ODN and DOX significantly reduced H22 tumor growth and extended the survival of tumor-bearing mice.Low-dose DOX could increase the proportion of T cells and CD69＋T cells in PBMCs,as well as the expression of CD107a and IFN-γin NK cells.DOXt-reated H 22 cells increased the proportion of T cells.Conclusion：Targeted blocking STAT3 could enhance the sensitivity of liver cancer cells to doxorubicin.So,combination therapy may improve DOX therapeutic effect and reduce DOX-mediated side effects.Furthermore,low dose of DOX can promote the activation of host immune system by acting on tumor cells.

关 键 词：STAT3 DECOY 阿霉素 肝癌 

分 类 号：R446.61[医药卫生—诊断学]