重组人p53腺病毒注射液联合顺铂对卵巢癌细胞生长及凋亡的影响

目的:探讨重组人p53基因腺病毒(recombinant adenovirus-p53,rAd-p53)注射液联合顺铂(cisplatin, DDP)对卵巢癌细胞株生长及细胞凋亡的影响.方法:利用MTT、FCM和Western 印迹法比较单独采用rAd-p53、DDP及2者联合用药对卵巢癌细胞株SKOV-3和CAOV-3细胞生长抑制、细胞周期、细胞凋亡以及p53蛋白表达的影响.结果: rAd-p53注射液对卵巢癌细胞株的生长有抑制作用,并呈时间、剂量依赖性关系;联合用药对卵巢癌细胞株生长抑制作用更显著(P<0.01),联合用药时不同的用药顺序对卵巢癌细胞株生长抑制无明显差异(P>0.05).联合用药72 h后,卵巢癌细胞株细胞周期明显阻滞于G0/G1期,S期比例明显减少,且细胞凋亡率显著升高(P<0.01).rAd-p53作用于卵巢癌细胞株72 h后,有明显的p53蛋白表达.结论:rAd-p53能将外源性野生型p53基因导入卵巢癌细胞基因组,使之表达p53蛋白,从而使肿瘤细胞的细胞周期阻滞于G0/G1期,抑制细胞生长,并促进细胞凋亡.rAd-p53与DDP联合应用,其抗肿瘤效应较单药用药更加显著.

Effects of domestic recombinant adenovirus p53 injection combined with cisplatin on growth and apoptosis of ovarian carcinoma cell lines

Objective:To evaluate the effects of domestic recombinant adenovirus p53 injection (rAd-p53,Gendicine) combined with cisplatin (DDP) on growth and apoptosis of ovarian carcinoma cell lines. Methods:MTT assay, flow cytometry, and Western blotting were used to compare the effects of rAd-p53, DDP and their combination on the growth, cell cycle, apoptotic rate, and p53 protein expression of ovarian carcinoma cell lines. Results:rAd-p53 inhibited ovarian carcinoma cells proliferation in dosE- and timE-dependent manners. After combined treatment, the growth inhibition rate was significantly increased (P<0.01). There was no significant diffE-rence in the inhibition potency induced by combined treatment with different sequences (P>0.05). Combined treatment significantly arrested ovarian carcinoma cell lines in G0/G1 phase at 72 h, the cell number in S phase was significantly decreased and the apototic rate was significantly increased (P<0.01). High expression of p53 protein was detected in ovarian carcinoma cell lines at 72 h after administeration of rAd-p53. Conclusion:rAd-p53 tranfects the exogenous widE-type p53 into the genome group of human ovarian tumor cells, induces p53 protein expression, thereby arresting tumor cells at G0/G1 phase, inhibiting tumor growth, and inducing apoptosis.