外源性野生型p53基因在两个肺腺癌细胞系中表达及对p16和p21基因的调控  

Research on expression and control of p16 and p21 by wild-type p53 gene in two lung adenocarcinoma cell lines

作　　者：金焰[1] 阎承慧[1] 吴焱[1] 刘艳[1] 张贵寅[1] 李璞[1] 傅松滨[1] 

机构地区：[1]哈尔滨医科大学遗传学与细胞生物学教研室,150086

出　　处：《中华医学遗传学杂志》2003年第5期409-412,共4页Chinese Journal of Medical Genetics

基　　金：黑龙江省科学技术计划攻关和青年科学基金 ( Q98- 9);黑龙江省科学技术计划攻关项目( G99C2 0 - 6 - 1 )

摘　　要：目的　探讨 p 53基因在肺癌细胞周期中的作用机制 ,以及裸鼠体内基因治疗的作用。方法　用以腺病毒为载体的野生型 p53基因 p Ad CMV-p53 (Ad-p53 )感染高转移肺腺癌 95D细胞系和高浸润肺腺癌 L -18系 ,对感染前后各细胞系的细胞生长曲线、p 53、p16和 p2 1基因的表达以及调亡进行分析。此外 ,用 Ad-p53对两细胞系进行了裸鼠体内感染实验。结果　体外实验中 ,导入 p 53基因细胞系的生长均得到抑制 ,并且最终都出现凋亡 ,感染后的细胞中 p53和 p 2 1基因的 m RNA表达量明显增高 ,p16基因的m RNA表达量则无明显变化。p53基因治疗后的裸鼠 ,其中 95D细胞系的肿瘤全部消失 ;L-18细胞系的腹腔注射组肿瘤全部消失 ,而皮下注射组无明显变化。结论　 p53基因是一个有效的肿瘤抑制基因 ,其诱导细胞凋亡的途径与 p16基因不同。腺病毒介导的野生型Objective: To evaluate the potentinal of p53 gene therapy for lung cancer in nude mice. Methods: Two lung adenocarcinoma cell lines L-18 and 95D were infected with adenovirus encoding wild-type p53 gene pAdCMV-p53(Ad-p53) in vitro and in vivo. The antitumor effect of wild-type p53 gene was assessed by cell growth curve, reverse transcriptase-polymerase chain reaction (RT-PCR) analysis and TUNEL staining methods. Results: The p53-specific growth inhibition and apoptosis of tumor cells were observed in both cell lines in vitro. By RT-PCR analysis, the increasing expression of p21 gene but not of p16 gene after p53 gene infection suggested that p21 gene played an important role in p53 gene induced cell apoptosis. The in vivo study revealed that celiac injection of p53 gene significantly inhibited the tumorigenesis in 95D and L-18 cells in nude mice. However, no obvious inhibition of tumorigenesis was observed after subcutaneous injection of p53 gene in L-18 cell line, compared with the inhibition noted in 95D cell line. Conclusion: The results showed the adenovirus-mediated antitumor therapy by means of p53 gene infection might be a potential way to inhibit cancer growth and induce tumor cell apoptosis.

关 键 词：肺腺癌 基因表达 基因转染 肿瘤抑制基因 p53 pl6 P21 

分 类 号：R734.2[医药卫生—肿瘤]