小片段RNA干扰提高人卵巢癌耐药细胞对化疗药物的敏感性研究

目的采用针对多药耐药基因MDR1的小片段RNA(siRNA)转染人卵巢癌耐药细胞株,了解转染后能否提高细胞对化疗药物的敏感性。方法用脂质体将合成针对MDR1的siRNA转染具有MDR1高表达的人卵巢癌泰素耐药细胞株OVCAR8/TR,并用ATP生物发光法检测转染前、后细胞对顺铂、5-氟脲嘧啶、阿霉素和泰素4种化疗药物敏感性的变化。结果OVCAR8/TR细胞对顺铂、阿霉素和泰素均耐药,转染后细胞能够明显提高通过P-gp转运药物泰素和阿霉素的敏感性,泰素对细胞的抑制率由转染前的26%提高到78%,阿霉素对细胞的抑制率则由转染前的37%提高到58%,对顺铂的耐药性则没有改变。单用脂质体转染组的药敏结果与未转染组差异无统计学意义。结论siRNA干扰能够逆转人卵巢癌化疗药物的多药耐药,提高对化疗药物的敏感性。

Improve the Chemosensitivity of Resistant Ovarian Cancer Cell by Small RNA,Interference

Objective To investigate the effects of siRNA on the drug resistance reversal of ovarian cancer cell.Methods The siRNA was transfected into human ovarian cancer cell line OVCAR8/TR by liposome.ATP-bioluminence assay was applied to measure the drug sensitivity to four chemotherapeutic agents before and after transfection.Results ATP-bioluminence assay showed that OVCAR8/TR cells were resistant to cDDP, ADM and Taxol. After siRNA transfection, OVCAR8/TR cells were sensitive to ADM and Taxol which are tansported by P-gp. The inhibition rate of ADM was improved from 37% to 58%, and that of Taxol was improved from 26% to 78%. However, the resistance of OVCAR8/TR cells to cDDP was not reversed. Conclusion siRNA can effectively improve the drug resistance to chemotherapeutic agents which are transfered by P-gp.The RNA interference can reverse MDR1-mediated drug resistance in ovarian cancer cell.