人肺腺癌SPC-A1荷瘤裸鼠中RNAi靶向沉默FAK的作用  

RNA Interference Targeting Focal Adhesion Kinase Inhibited the Growth of Human Lung Adenocarcinoma SPC-A1

作　　者：叶璐 母丹 付波 王敏 杨莉 邓洪新[2] Ye Lu Mu Dan Fu Bo et al(Department of Oncology,No. 416 Hospital of Ministry of Nuclear Industry, Chengdu 610051, Sichuan, China)

机构地区：[1]核工业416医院肿瘤科,成都610051 [2]四川大学华西医院生物治疗国家重点实验室/2011计划"生物治疗协同创新中心",成都610041

出　　处：《肿瘤预防与治疗》2016年第6期303-309,共7页Journal of Cancer Control And Treatment

基　　金：国家"重大新药创制"科技重大专项(编号:2009ZX09102-241)

摘　　要：目的:通过用脂质体包裹靶向局部粘着斑激酶(focal adhesion kinase,FAK)基因的短发夹RNA(short hairpin RNA,shRNA)质粒(shRNA-FAK),探讨该方法对荷瘤裸鼠中人肺腺癌SPC-A1的抑制效果。方法:用脂质体包裹shRNA-FAK,并通过尾静脉注射治疗荷瘤裸鼠,通过肿瘤生长曲线和重量,肿瘤组织形态学,肿瘤中的FAK蛋白表达情况、CD31、VEGF、PCNA和TUNEL检测,分析该方法对荷瘤裸鼠中人肺腺癌SPC-A1的抑制效果。结果:荷瘤裸鼠经过脂质体shRNA-FAK治疗后,肿瘤生长速度明显缓于对照组(P<0.05),肿瘤重量明显低于对照组(P<0.05)。肿瘤组织的免疫组化、western blot和TUNEL检测显示与对照组相比,治疗组FAK蛋白表达降低(P<0.05)、血管生成和细胞增殖均减少(P<0.05)、凋亡细胞增加(P<0.05),荷瘤裸鼠主要脏器形态学正常。结论:FAK特异性的小干扰RNA(small interfering RNA,siRNA)能够在体内阻断FAK蛋白的表达,使组织内FAK蛋白的表达相应地减少,并进一步诱导肿瘤细胞的凋亡,最终导致肿瘤的生长速度减缓。Objective： To evaluate the inhibition effect of the plasmids encoding focal adhesion kinase （FAK） short hairpin RNA （shRNA） encapsulated in liposome on human lung adenocarcinoma SPC-A1 in nude mice bearing tumor. Meth- otis： The nude mice bearing tumor were established and treated with shRNA-FAK encapsulated in liposome through tail vein injection. The inhibition effect of human lung adenocarcinoma SPC-A1 in nude mice was analyzed by tumor growth curve and weight, tumor histomorphology, FAK protein expression, CD31, VEGF, PCNA and TUNEL detection. Results： Tumor growth speed was significantly slower in the nude mice treated with liposomal shRNA-FAK than that in the control group （ P 〈 O. 05）. The tumor weight in the nude mice treated with liposomal shRNA-FAK was significantly lower than that of the control group（P 〈0.05）. Immunohistochemistry, Western blot and TUNEL assay showed that the expression of FAK protein（P 〈 0. 05 ）, the angiogenesis and cell proliferation decreased （ P 〈 O. 05 ）, and the apoptotic cells increased （ P 〈 O. 05 ） in the treatment group compared with the control group, and the main organs of the nude mice bearing tumor were morphologically normal. Conclusion： FAK-specific small interfering RNA （siRNA） can suppress the expression of FAK protein in vivo, and the expression of FAK protein in the tissue is correspondingly reduced, thus induces the apoptosis of tumor cells, leading to the decelerated tumor growth.

关 键 词：RNA干扰 局部粘着斑激酶 凋亡 SPC-A1 

分 类 号：R734.2[医药卫生—肿瘤] R73-35[医药卫生—临床医学]