化疗药物对甲状腺未分化癌耐药基因表达的影响

Expression of MDRl and MRP1 in anaplastic thyroid carcinoma cell line HTh74 after chemotherapeutical drug intervention

目的:评价阿霉素和顺铂化疗药物对甲状腺未分化癌耐药相关基因MDR1和MRP1表达的影响。方法:分别用阿霉素和顺铂诱导人甲状腺未分化癌耐药细胞HTh74/DOX和HTh74/DDP。利用荧光定量RT-PCR检测耐药细胞中MDR1和MRP1的表达情况,并观察MDR1和MRP1抑制剂联合阿霉素或顺铂对耐药细胞进行干预的疗效。结果:HTh74/DOX细胞与亲代相比高表达MDR1而MRP1基因上调不明显;HTh74/DDP细胞与亲代相比高表达MRP1基因而MDR1基因上调不明显,且HTh74/DOX对顺铂缺乏交叉耐药,HTh74/DDP对阿霉素缺乏交叉耐药。MDR1和MRP1抑制剂分别能部分恢复HTh74/DOX和HTh74/DDP对阿霉素和顺铂的敏感性。结论:不同化疗药物可能上调不同ABC跨膜转运蛋白耐药相关基因而导致甲状腺未分化癌细胞耐药性增强。临床可能通过检测各种ABC跨膜转运蛋白或基因的表达量来预测不同化疗药物的疗效,并选用适当ABC跨膜转运蛋白抑制剂联合化疗药物进行个体化治疗方案的制定。

Objective：To evaluate the correlation of doxorubicin and cisplatin intervention with the expression levels of MDR1 and MRP1 in anaplastic thyroid carcinoma cell line HTh74.Methods：Doxorubicin resistant cells（HTh74 / DOX） and cisplatin resistant cells（HTh74 / DDP） were obtained by treating the HTh74 cell with doxorubicin or cisplatin for 6 months respectively.Fluorescent quantitative RT-PCR was adopted to detect the transcription of MDR1 and MRP1 in HTh74 / DOX and HTh74 / DDP.Results： Compared to their parental HTh74 cell,HTh74 / DOX cell expressed high level of MDR1 and low level of MRP1,HTh74 / DDP expressed high level of MRP1 and low level of MDR1.HTh74 / DOX cells lacked cross resistance to cisplatin,and HTh74 / DDP cells lacked cross resistance to doxorubicin.Inhibitors of MDR1 or MRP1 partly restored the toxicity of doxorubicin or cisplantin on the resistant cells respectively.Conclusion：Different chemotherapeutics increase the expression of different ABC transporters to enhance the drug resistance.Detecting the expression of ABC transporters can be used to predict the effect of chemotherapeutic drugs in clinical.The proportionate inhibitor of ABC transporter combined with chemotherapeutic drugs may be effective in individual treatment.