Ad-ING4对人大细胞肺癌NCI-H460细胞移植瘤抑癌效应的体内实验研究  

Experimental study on growth suppression of NCI-H460 transplantation tumor by Ad-ING4 in vivo

作　　者：梁光辉 丁志丹[2] 李振轩 杨吉成[3] 赵军[4] 邢文群 Liang Guanghui;Ding Zhidan;Li Zhenxuan;Yang Jicheng;Zhao Jun;Xing Wenqun(Department of Thoracic Surgery,Affiliated Cancer Hospital of Zhengzhou University,Zhengzhou 450008,China;Department of Thoracic Surgery,the First Affiliated Hospital of Zhengzhou University,Zhengzhou 450052,China;Department of Cell and Molecular Biology,School of Basic Medicine,Suzhou University,Suzhou 215123,China;Department of Cardiothoracic Surgery,the First Affiliated Hospital of Soochow University,Suzhou 215000,China)

机构地区：[1]郑州大学附属肿瘤医院胸外科,450008 [2]郑州大学第一附属医院胸外科,450052 [3]苏州大学基础医学院细胞与分子生物学教研室,215123 [4]苏州大学附属第一医院心胸外科,215000

出　　处：《中华实验外科杂志》2021年第7期1295-1299,共5页Chinese Journal of Experimental Surgery

摘　　要：目的:探讨腺病毒介导的ING4基因表达对NCI-H460肺癌细胞裸鼠移植瘤的抑癌增效作用及分子机制。方法:用Ad-ING4重组腺病毒在裸鼠NCI-H460移植瘤的瘤体内注射治疗,观察肿瘤生长变化,治疗结束后3 d处死裸鼠、摘取瘤体并称瘤体重量;免疫组织化学检测瘤体组织中B细胞淋巴瘤/白血病-2相关X蛋白(bax)、半胱氨酰天冬氨酸特异性蛋白酶(Caspase)-3、B细胞淋巴瘤/白血病-2(bcl-2)、生存素(Survivin)等相关因子的表达。组间数据比较采用t检验。结果:动物实验结果表明,Ad-ING4组的平均体积明显低于磷酸盐缓冲液(phosphate buffer saline,PBS)对照组(720.20±23.51,t=30.64,P<0.05)和Ad-GFP空病毒组(469.90±32.57,t=14.43,P<0.05),差异有统计学意义;平均瘤体重量明显低于Ad-GFP组(0.732±0.068,t=9.26,P<0.01)和PBS组(0.757±0.049,t=15.32,P<0.05),差异有统计学意义;Ad-ING4重组腺病毒能显著抑制裸鼠NCI-H460移植瘤的生长,瘤重的抑制率达32.69%,与空病毒载体Ad-GFP组和细胞对照PBS组比较差异有统计学意义(P<0.05);免疫组织化学结果显示Ad-ING4重组腺病毒能明显上调bax和Caspase-3蛋白的表达水平,下调bcl-2和Survivin蛋白的表达水平。结论:腺病毒介导的IL-24基因可明显抑制人肺癌细胞NCI-H460移植瘤的生长,诱导其凋亡,其分子机制可能与上调bax、Caspase-3等促凋亡因子的表达,下调bcl-2、Survivin等凋亡抑制因子的表达有关。Objective To study the enhanced anticancer effect and its mechanism by Ad-ING4-polyA+promoter(Ad-ING4)for lung cancer transplantation tumor(NCI-H460).Methods Anti-tumor experiment was conducted on these mice bearing lung cancer transplantation of NCI-H460 cells by intratumoral injection with the recombinant adenovirus.Tumor growth was recorded by volume.All tumors were taken out and weighed at 3rd day after treatment.The expression levels of cytokines including B cell lymphoma/leukemia-2 associated X protein(bax),cysteinyl aspartate-specific protease(Caspase)-3,B cell lymphoma/leukemia-2(bcl-2)and Survivin were detected by immunohistochemisty.The data were compared between groups by t-test.Results Animal experimental results showed that the average volume in Ad-ING4 group was significantly smaller than that in PBS group(720.20±23.51,t=30.64,P<0.05)and Ad-GFP group(469.90±32.57,t=14.43,P<0.05).The average tumor weight was significantly milder in Ad-ING4 group than in Ad-GFP group(0.732±0.068,t=9.26,P<0.01)and PBS group(0.757±0.049,t=15.32,P<0.05).Tumor growth was significantly inhibited in the Ad-ING4 group as compared with that in the Ad-GFP group and the PBS group(P<0.05).The weight inhibitory rate was 32.69%in the Ad-ING4 group.The expression levels of bax and Caspase-3 were up-regulated,and those of bcl-2 and Survivin were downregulated in the Ad-ING4 group.Conclusion It is proved that there is enhanced anticancer effect by Ad-ING4.The mechanism may be related to the up-regulations of bax and Caspase-3,and the down-regulations of bcl-2 and Survivin.

关 键 词：肺癌 腺病毒载体 肿瘤抑制 

分 类 号：R734.2[医药卫生—肿瘤]