外源性p73基因对wtp53型人肺腺癌细胞A549化疗敏感性的影响

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

目的 研究外源p73基因转染wtp5 3型人肺腺癌A5 49细胞对其化疗药物敏感性的影响。 方法 用脂质体介导的转染技术 ,将含有全长人野生型 p73αcDNA和野生型 p5 3cDNA的真核表达重组质粒分别导入A5 49细胞 ,观察基因转染前后肿瘤细胞对化疗药物顺铂和阿霉素敏感性的变化。结果 A5 49 p73α细胞可以稳定地表达P73α蛋白 ,其生长速度较未转染p73α和转染wtp5 3基因的A5 49细胞明显减慢 ,克隆形成数下降 ,凋亡细胞明显增多。与未转染组比较 ,在原本没有抑制和杀伤作用的化疗药物浓度作用下A5 49 p73α细胞生长明显受到抑制 ,顺铂和阿霉素的IC50 值分别降低为约 1/6和 1/70。结论 研究显示外源性 p73基因的导入增加了wtp5 3型人肺腺癌A5 49细胞对顺铂和阿霉素等化疗药物的敏感性 ,为 p73基因用于治疗wtp5

Objective 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 IC 50 values for DDP and ADM were reduced to approximate 1/6 and 1/70 in A549 p73α cells compared with A549 cells respectively. Conclusion 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.