6种常见耐药标志物在氟尿苷耐药绒癌细胞系构建过程中的动态表达

Dynamical mRNA Expression Profiles of Six Common Chemo-resistance Related Genes in Floxuridine-resistance Human Choriocarcinoma JEG-3 Cell Line

目的:通过检测对氟尿苷(FUDR)耐药的绒癌细胞系构建过程中肺耐药相关蛋白(LRP)、二氢叶酸还原酶(DHFR)、survivin、谷胱甘肽S-转移酶-π(GST-π)、多药耐药基因(MDR1)和多药耐药相关蛋白基因(MRP)6种常见耐药标志物的动态表达,探讨其耐药机制并进行耐药标志物的初步筛选。方法:用化学发光法和荧光定量PCR技术,分别检测不同浓度FUDR诱导的JEG-3细胞中β-人绒毛膜促性腺激素(β-HCG)的分泌量和上述6种常见耐药标志物在耐药细胞构建过程中的动态表达。结果:不同基因在药物诱导过程中的变化趋势不尽相同。只有LRP基因的表达随着诱导药物浓度和肿瘤细胞耐药性的增加而逐渐上调。结论:耐药的产生是分阶段的,不同阶段有不同的因素参与。就目前的研究结果而言,只有LRP的表达变化与FUDR诱导浓度和耐药性有明显正相关,提示其可以作为绒癌对FUDR耐药的候选预测指标。

Objective：To assess whether the transcript level of lung resistance-related protein （LRP）, dihydrofolate reductase（ DHFR）, glutathione-S-transferase-π （GST-π）, multidrug resistance gene （ MDR1 ） multidrug resistance protein （MRP） and survivin can be used for screening the floxuridine（FUDR） -based chemoresistant biomarker. Methods：Quantitative RTPCR was used to measure these six genes mRNA expression in JeG -3 cell lines during different concentrations of FUDR-exposureo 13 subunit human chorionic gonadotropin （β-HCG） in the culture medium was detected by chemo-luminescence. Results：The changing tendency of the different genes were different,only LRP gene showed gradual upregulation when the concentration or chemoresistance of Floxuridine increased. Conclusions： The genesis of chemoresistance is step by step, and variable factors are involved in different stages. From this pilot study,only the expression change of LRP is coincident with the concentration and chemoresistance of Floxuridine,so it can be a candidate prognostic marker for detecting chemoresistance in choriocarcinoma patients.