[外源性p73基因对野生型p53人肺腺癌细胞A549化学敏感性的影响]

[Effect of exogenous p73 gene on chemosensitivity of wild-type p53 human lung adenocarcinoma cell A549].

作者信息

He Yong, Fan Shizhi, Jiang Yaoguang, Chen Jianming, Li Zhiping, Zhou Ping, Zhou Yuanguo

机构信息

Thoracic Surgery Center of People's Liberation Army, Daping Hospital/The Research Institute of Surgery, The Third Military Medical University, Chongqing 400042, P.R.China.

出版信息

Zhongguo Fei Ai Za Zhi. 2004 Aug 20;7(4):331-5. doi: 10.3779/j.issn.1009-3419.2004.04.15.

DOI:10.3779/j.issn.1009-3419.2004.04.15

PMID:21241554

Abstract

BACKGROUND

To assess the effects of exogenous p73 gene on chemosensitivity of wild-type p53 human lung adenocarcinoma cell A549 to cisplatin (DDP) and adriamycin (ADM).

METHODS

Recombinant eukaryotic expression vector pcDNA3 containing full-length human wild-type p73α cDNA or p53 cDNA was transfected into A549 cells which had wtp53 by lipofectamine-mediated gene transfection. The chemosensitivity of tumor cells to DDP and ADM was observed before and after transfection.

RESULTS

A549-p73α could stably express P73α protein. The P73α protein expression was significantly increased in A549-p73α than that in A549 and A549-pcDNA3. The growth and colony formation of A549-p73α were significantly inhibited compared with A549, A549-pcDNA3 and A549-wtp53. Flow cytometry and DNA fragmentation analysis showed apoptosis of A549-p73α cells was significantly increased. The IC₅₀ values for DDP and ADM were reduced to approximate 1/6 and 1/70 in A549-p73α cells compared with A549 cells respectively..

CONCLUSIONS

Exogenous p73 gene is capable of enhancing the sensitivity of wild-type p53 human lung adenocarcinoma cell A549 to chemotherapeutic drugs. It is probably for p73 to be used in the treatment of p53-resistant tumors.

摘要

背景

评估外源性p73基因对野生型p53人肺腺癌细胞A549对顺铂（DDP）和阿霉素（ADM）化疗敏感性的影响。

方法

通过脂质体介导的基因转染，将含有全长人野生型p73α cDNA或p53 cDNA的重组真核表达载体pcDNA3转染至具有野生型p53的A549细胞中。观察转染前后肿瘤细胞对DDP和ADM的化疗敏感性。

结果

A549-p73α能够稳定表达P73α蛋白。A549-p73α中P73α蛋白表达明显高于A549和A549-pcDNA3。与A549、A549-pcDNA3和A549-wtp53相比，A549-p73α的生长和集落形成受到明显抑制。流式细胞术和DNA片段化分析显示A549-p73α细胞凋亡明显增加。与A549细胞相比，A549-p73α细胞中DDP和ADM的IC₅₀值分别降至约1/6和1/70。