HER2 RNA干扰与TGF-β1中和联合应用提高荷瘤小鼠生存率  

TGF-β1 neutralization combined HER2 silencing enhance survival rate of tumor-bearing mice

作　　者：曾瑞[1] 邹丽云[2] 张晋宇[2] 王芳[3] 贾正才[3] 阮志华[1] 

机构地区：[1]第三军医大学西南医院肿瘤科,重庆400038 [2]第三军医大学西南医院基础部免疫学研究所,重庆400038 [3]第三军医大学西南医院科研部生物医学分析测试中心,重庆400038

出　　处：《免疫学杂志》2014年第4期277-281,292,共6页Immunological Journal

基　　金：国家自然科学基金(31170850)

摘　　要：目的探讨提高癌基因HER2 RNA干扰抑瘤效果的新方法。方法采用RNA干扰抑制B16细胞中癌基因HER2的表达后,体外分析HER2 RNA干扰对B16细胞的增殖、老化、凋亡和细胞周期的影响。用TGF-β1中和抗体腹腔注射C57BL/6小鼠,皮下接种HER2 RNA干扰后肿瘤细胞或对照细胞,检测血清中游离TGF-β1的含量、观察荷瘤小鼠生存情况。结果与对照相比,HER2 RNA干扰后B16细胞的增殖速度显著下降,细胞凋亡率和G2/M期细胞明显增加,而细胞的老化则无显著变化。体内实验发现,TGF-β1中和抗体对接种了对照肿瘤细胞的小鼠的生存率无明显影响;与接种了对照肿瘤细胞的小鼠相比,接种了HER2RNA干扰肿瘤细胞的小鼠生存率有一定程度的提高,TGF-β1中和抗体则进一步提高了接种HER2 RNA干扰肿瘤细胞的小鼠生存率。结论癌基因HER2的RNA干扰可通过抑制细胞分裂、促进细胞凋亡等抑制B16细胞的增殖,TGF-β1中和与HER2 RNA干扰联合应用可显著提高荷瘤小鼠的生存率。As overexpression of oncogene HER2 is associated with aggressive clinical progression of several tumors, HER2 inhibition has been applied to the treatment of tumors with high HER2 levels, but the efficacy is limited. In this study, we investigated the feasibility of improving the anti-tumor efficiency of HER2 inhibition by TGF-β1 neutralization. The results showed that down-regulation of HER2 expression by RNA interference promoted the cell apoptosis and increased GJM-phase proportion of B16 mouse melanoma cells, while cell ageing did not change much. And, the HER2 silencing suppressed the B16 cell proliferation in vitro. After inoculated with B16 cells with or without TGF-β1 neutralization, C56BL/6 mice inoculated with HER2 silenced B16 cells had a higher survival rate than that of mice inoculated with the controls, and TGF-β1 neutralization could further increased the survival rate of mice inoculated with HER2 silenced B16 cells. On the contrary, TGF-β1 neutralization could not prolong the survival of mice inoculated B16 cells without HER2 silencing. Our results indicate that RNAi-mediated HER2 silencing is capable of inhibiting the proliferation of melanoma cells through promoting apoptosis and inducting G2/M cell cycle arrest. And the neutralization of TGF-β1 can enhance the anti- melanoma efficiency of HER2 silencing and thus improve the survival rate of tumor-bearing mice. This study may provide a base for the study of tumor therapy based on oncogene silencing.

关 键 词：TGF-Β1 HER2 RNA干扰 黑色素瘤 

分 类 号：R730.5[医药卫生—肿瘤]