乏氧状态下外源性野生型p53基因对肺癌细胞照射敏感性的影响

目的 将重组人外源性野生型p53(wtp53)基因的腺病毒转染人肺腺癌细胞系(A549),在乏氧状态下舰察wtp53基因对A549细胞照射后存活的影响.方法 实验分为有氧状态下单纯照射组、照射+wtp53基因转染组,乏氧状态下单纯照射组、照射+wtp53基因转染组.给予9MeV电子束照射0、2、4、6、8、10 Gy,测定克隆形成率,用多靶单击模型拟和生存曲线,计算D0、Dq值和氧增强比(OER)、p53基因照射增敏比(SER).流式细胞仪检测4个组细胞凋亡率.结果 单纯照射时OER=1.75,转染wtp53后OER=0.81.有氧状态下wtp53的SER=1.77,乏氧状态下wtp53的SER=3.84.细胞凋亡率:未转染p53基因时,乏氧照射低于有氧照射组(F=7.92,P=0.048);有氧照射时单纯照射低于照射+wtp53基因转染组(F=52.44,P=0.001),乏氧照射时单纯照射低于照射+wtp53基因转染组(F=82.50,p=0.001);有氧照射+wtp53基因转染组和乏氧照射+wtp53基因转染组的凋亡率相似(t=2.04,P=0.111).结论 乏氧能够增加肺癌细胞埘照射的抗拒性.wtp53基因可以促进乏氧状态下的A549细胞的凋亡和提高放射敏感性.

Exogenous wild type p53 gene affects radiosensitivity of human lung adenocarcinoma cell line under hypoxia

Objective To evaluate the effect of exogenous wild type p53 (wtp53) gene on radiosensitivity of human lung adenoeareinoma cell line under hypoxia. Methods Human lung adenoeareinoma cell line A549 was transfected with adenovirus carrying recombinant exogenous wtp53. Four irradiation groups were studied : normal cell ( Group A), wtp53 transfeeted cell ( Group B ), normal cell under hypoxia (Group C) and wtp53 transfected cell under hypoxia( Group D). Ceils were irradiated with 9 MeV electron beams. Cellular survival fraction was analyzed. Multi-target single-hit model was used to plot the survival curve. D0,Dq ,oxygen enhancement ratio(OER) ,sensitizing enhancement ratio(SER) and other parameters were used to evaluate the effects of wtp53 gene on radiosensitivity of A549. The cell apoptotie rate of each group was examined by flow eytometry. Results OER was 1.75 and O. 81 before and after wtp53 transfeetion. SER was 1.77 in oxic circumstance and 3.84 under hypoxia. The cell apoptotie rate of Group A and B was lower than Group C and D(F=7.92 ,P=0.048) ,with Group A lower than B and Group C lower than D (F=82.50,P=0.001). But Group B and D were similar(t=2.04,P=0. 111). Conclusions Hypoxia can increase the radiation resistance of lung adenoeareinoma cell line .4,549. The wtp53 can promote apoptosis and improve tumor radiosensitivity,especially under hypoxia.