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

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

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。

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 MDRl-mediated drug resistance in ovarian cancer cell.