Ad-p53对乳腺癌细胞雌激素受体表达的影响

Influence of ER expression by Ad-p53 processing in breast cancer

目的:探讨肿瘤基因治疗药物重组人p53腺病毒注射液(Ad-p53)治疗乳腺癌存在无效病例与雌激素受体(ER)同p53相互作用的关系。方法:采用Western blot检测技术,观察不同浓度、不同作用时间Ad-p53对乳腺癌MCF-7细胞ER状态的影响及ER与p53的相互作用。结果:不同浓度(0、1、10、100、1000、10 000 MOI)Ad-p53处理MCF-7细胞48 h后,10～100 MOI时ER表达存在高峰。调整Ad-p53浓度(0、10、30、50、80、100 MOI)处理48 h后,0～80 MOI时ER及p53表达逐渐增加,80～100 MOI时p53表达继续增加,ER明显减少。继续相同Ad-p53浓度(0、10、30、50、80、100 MOI)处理,时间缩短为24 h,ER表达趋势相同,但在各浓度下,ER表达量均减少。结论:Ad-p53能够促进乳腺癌ER的表达,但随着ER表达增加,p53与ER相互制约使ER表达受到抑制而逐渐下降,有望通过调节ER状态找到Ad-p53个体化治疗乳腺癌的理论依据。

Objective： Investigate the relationship of p53 and ER＇s reaction and invalid case what be processed by Ad-p53. Methods： Western blot was used to detect the expression of ER in MCF-7 cells by Ad-p53 processing at different time. Results： There was a peak value of ER ex- pression in 10-100 MOI （MOI： multiplicity of infection） after 48 of Ad-p53 processing with different concentration （0, 1, 10, 100, 1 000, 10 000 MOI）. Then, we adjusted the Ad-p53 （0, 10, 30, 50, 80, 100 MOI） but was 48 hours constantly, the expression of ER and p53 all increased at 0N80 MOI, and the p53 still increase but ER decreased apparently in 100 MOI. Finally, curtailed the processing time to 24 hours, we got the same result of ER, but the expression reduced in all concentration. Conclu. s/on： If Ad-p53 was in a certain range （in the ON100 MOI）, ER expression level follow Ad-p53 in- creased, when exceeding this range ER expression gradually decreased, and the 48 hours was the peak effect of Ad-p53. As the result, rAd-p53 can promote ER expression in breast cancer, but ER expres- sion was suppressed and decreased with p53 and ER interaction relationship when ER was too much. This study confirmed the reaction between Ad-p53 and ER in breast cancer cells in vitro. The next study that regulate ER to find the combined treatment of Ad-p53 is following this theoretical basis.