重组人p53腺病毒在乳腺癌裸鼠体内耐药逆转作用及其对P-糖蛋白表达的影响

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MCF4/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.

Effect of adenovirus-mediated p53 gene therapy on reversing multidrug resistance in breast cancer in vivo and its effect on expression of P-gp

Objective To study the effect of recombinant adenovirus mediated p53 gene on reversing multidrng 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 ＋ adria- mycin. The growth of tumor was observed. Expression of P-gp in several groups was assessed by Western blotting. Results The inhib- itory rate after administration of rAd-p53, adriamycin, and rAd-p53 ＋ adriamyein 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 ＋ adria- mycin was more significant than inhibition in group rAd-p53 and group adriamycin. The expression of P-gp in groups of control, rAd- p53, adriamyein, rAd-p53 ＋ adriamycin were （0. 5964± 0. 0806 ）, （ 0. 5506 ± O. 0127 ）, （ 0. 5641±0. 0055 ）, and （ 0. 4652 ± 0. 0982）, respectively it was decreased significantly in group rAd-p53 ＋ Adriamycin. Conclusions tAd-p53 can effectively reverse the multidrng resistance of MCF-7/ADR xenografts in nude mice. And it can inhibit the expression of P-gp.