腺病毒介导野生型p53基因对人肺腺癌细胞的抑制效应

目的：p53基因突变是人类肿瘤中常见的遗传学改变。将野生型p53基因导入一些肿瘤细胞中被证明能抑制其细胞增殖,因此做为肺癌基因治疗主要目的基因而备受关注。本研究旨在观察野生型p53基因对人肺腺癌细胞和裸鼠移植瘤的抑制效应,并对其抑癌机制进行分析,为今后肺癌基因治疗的临床试验提供科学依据。方法：采用重组体腺病毒Ad-p53基因转染人肺腺癌细胞系GLC－82;以裸鼠皮下移植瘤治疗试验观察Ad-p53基因的抑瘤效应;用流式细胞计数,DNA片断化及TUNEL分析探讨Ad-p53基因的抑癌机制。结果：导入Ad-p53基因后人肺腺癌GLC－82细胞生长能力显著下降,克隆形成能力受到明显抑制;并显著抑制裸鼠皮下移植瘤的生长;肺癌细胞发生凋亡,并出现明显的G1期阻滞现象。结论：腺病毒介导野生型p53基因（Ad-p53)对人肺腺癌细胞和裸鼠皮下移植瘤均有明显抑制效应,主要通过诱导癌细胞凋亡和参与细胞周期调控实现,进而提示Ad-p53基因有可能在人肺癌基因治疗中发挥重要作用。

The Growth Inhibit Effect Mediated by Wild- type p53 Adenovirus Gene Transfer in Human Lung Adenocarcinoma Cell

Objective:Mutations of the p53 tumor suppressor gene are the most common genetic alternation in human cancer.It is proved that the growth of lung cancer cells can be inhibited when the cells were transduced by wild-type p53 gene.Thus,as a promising therapeutic gene for lung cancer gene therapy,p53 gene has already become a hot spot.This study is to investigate the inhibitory effect on human lung adenocarcinoma cells by wild-type p53 in vitro/in vivo and to explore the molecular mechanism of its anti-cancer,in an attempt to contributing to the scientific basis of clinical trials in gene therapy for lung cancer.Methods:A wild type p53-expressing adenovirus(Ad-p53)was transferred into the human lung adenocarcinoma cell line GLC-82;Using experimental therapy on the nude mice model bearing subcutaneous tumor of GLC-82 cells,the anti-tumor effect by Ad-p53 was observed;The anti-cancer mechanism was analyzed through the analysis of flow cytometry,DNA fragmentation and TUNEL techniques.Results:The growth and the colony formation of the transduced cancer cells were greatly inhibited by Ad-p53,and the growth of nude mice transferred tumors was highly suppressed.The analysis of flow cytometry,DNA fragmentation and TUNEL techniques showed that the transduced cancer cells were induced apoptosis and G1 arrest.Conclusion:Ad-p53 can greatly inhibit the growth both of human lung adenocarcinoma cells and nude mice transferred tumors,its anti-cancer effects result mainly from apoptosis and G1 arrest.Ad-p53 may play an important role in lung cancer gene therapy.