目的 研究重组人p53腺病毒(rAd-p53)对人乳腺癌MCF-7/ADR裸鼠移植瘤的耐药逆转作用及其对耐药相关P-糖蛋白(P-glycoprotein, P-gp)表达的影响。方法 建立人乳腺癌MCF-7/ADR裸鼠耐药模型,随机分为对照组、rAd-p53组、阿霉素组、联合组,分别给予不同治疗。观察裸鼠肿瘤体积的变化, western blot检测P-gp蛋白表达情况。结果 成瘤后rAd-p53组、阿霉素组、联合组抑瘤率分别为42.05%、49.21%、69.97%,各治疗组体积与对照组相比差异有统计学意义(P＜0.05),且联合组显著优于rAd-p53组和阿霉素组(P＜0.05)。对照组、rAd-p53组、阿霉素组、联合组P-gp表达水平分别为(0.5964±0.0806)、(0.5506±0.0127)、(0.5641±0.0055)、(0.4652±0.0982),联合组P-gp表达水平低于其他各组。结论 Ad-p53对人乳腺癌阿霉素耐药细胞株MCF-7/ADR建立的裸鼠移植瘤具有多药耐药的逆转作用,并可下调P-gp的表达。

Objective To study the effect of recombinant adenovirus mediated p53 gene on reversing multidrug resistance and expression of P-gp in MCF-7/ADR human breast cancer xenografts. Methods MCF-7/ADR human breast cancer cells were injected into nude mice. The experimental mice with xenografts were randomized into groups of control, rAd-p53, adriamycin, rAd-p53+adriamycin. The growth of tumor was observed. Expression of P-gp in several groups was assessed by Western blotting. Results The inhibitory rate after administration of rAd-p53, adriamycin, and rAd-p53+adriamycin were 42.05%,49.21%, and 69.97%, respectively. There was significant difference between all treatment groups and control group (P＜0.05). And inhibition in group rAd-p53+adriamycin was more significant than inhibition in group rAd-p53 and group adriamycin. The expression of P-gp in groups of control, rAd-p53, adriamycin, rAd-p53+adriamycin were (0.5964±0.0806), (0.5506±0.0127), (0.5641±0.0055), and (0.4652±0.0982), respectively it was decreased significantly in group rAd-p53+Adriamycin. Conclusions rAd-p53 can effectively reverse the multidrug resistance of MCF-7/ADR xenografts in nude mice. And it can inhibit the expression of P-gp.