TRIM28shRNA联合依托泊甙抑制非小细胞肺癌裸鼠肿瘤生长的研究  

Study on TRIM28shRNA in combination with etoposide inhibits non-small cell lung cancer growth in nude mouse

作　　者：刘镭 赵长祺 王建平 赵学荣 高亚贤 程露阳 许倩 李庆宝 赵丽岑 LIU Lei;ZHAO Changqi;WANG Jianping;ZHAO Xuerong;GAO Yaxian;CHENG Luyang;XU Qian;LI Qingbao;ZHAO Licen(Teaching and Researching Section of Immunology,Chengde Medical College,Chengde,Hebei 067000,China;Experimental Center of Pathogen Biology,Chengde Medical College,Chengde,Hebei 067000,China;Research Institute of Basic Medicine,Chengde Medical College,Chengde,Hebei 067000,China)

机构地区：[1]承德医学院基础医学院免疫学教研室,河北承德067000 [2]承德医学院基础医学院病原生物学实验中心,河北承德067000 [3]承德医学院基础医学院基础医学研究所,河北承德067000 [4]承德医学院基础医学院,河北承德067000

出　　处：《重庆医学》2018年第34期4335-4339,共5页Chongqing medicine

基　　金：国家自然科学基金资助项目(81703001);河北省自然科学基金资助项目(H2015406014);河北省人才工程培养经费资助科研项目(A2016002085);河北省高等学校科学技术研究青年基金项目(QN2016141);河北省病原生物学重点学科项目

摘　　要：目的构建TRIM28短发夹RNA(shRNA)稳定干扰非小细胞肺癌(NSCLC)PAa细胞株,并探讨TRIM28shRNA联合依托泊甙对裸鼠移植瘤生长的影响和可能的机制。方法通过特异性shRNA慢病毒载体在PAa细胞中稳定干扰TRIM28表达;PAa细胞皮下注射建立裸鼠移植瘤模型,并应用TRIM28shRNA单独或联合依托泊甙进行治疗;应用末端脱氧核苷酸转移酶介导的dUTP缺口末端标记(TUNEL)测定法检测裸鼠移植瘤细胞凋亡情况和免疫组织化学技术检测移植肿瘤中E2F转录因子1(E2F1)的表达。结果成功构建了TRIM28shRNA稳定干扰的PAa细胞株;证实TRIM28shRNA联合依托泊甙能够显著抑制裸鼠肿瘤的生长;TRIM28shRNA联合依托泊甙明显诱导肿瘤细胞凋亡并诱导肿瘤组织表达E2F1蛋白。结论TRIM28shRNA联合化疗药物依托泊甙对抑制NSCLC肿瘤生长有明显效果。Objective To establish a non-small lung cancer cell line stably interfered by TRIM28 shRNA,and to explore the effect of TRIM28shRNA in combination with etoposide on nude mouse xenografts tumor growth and possible mechanism.Methods The expression of TRIM28 was stably interfered by specific shRNA lentiviral vector in PAa cell;the nude mouse model with NSCLC exnografts was established by PAa cell subcutaneous injection and treated by TRIM28 alone or in combination with etoposide;the apoptosis of nude mouse exnografts tumor was detected by TUNEL and the expression of E2F1 in tumor tissue was detected by immunohistochemistry.Results A PAa cell line stably interfered by TRIM28 shRNA was established successfully;it was verified that TRIM28shRNA in combination with etoposide could inhibit the nude mouse tumor growth significantly.TRIM28shRNA in combination with etoposide significantly induced tumor cell apoptosis and induced the expression of E2F1 in tumor tissue.Conclusion TRIM28shRNA in combination with chemotherapeutic drug etoposide has obvious effect on the growth of NSCLC.

关 键 词：癌 非小细胞肺 TRIM28 SHRNA 依托泊甙 裸鼠 

分 类 号：R734.2[医药卫生—肿瘤]