Upregulation of the ATP-binding cassette (ABC) transporter is one of the most important factors leading to multidrug resistance (MDR) in several types of cancer. In the present study, we investigated the ability of rucaparib, a Poly (ADP-ribose) polymerase (PARP) inhibitor which is currently in clinical development, on overcoming ABC transporters-mediated MDR in cervical cancer cell lines. Rucaparib significantly enhanced the cytotoxic effects of a series of conventional chemotherapeutic drugs in drug resistance cervical cancer cell lines. Moreover, rucaparib significantly increased the accumulation of rhodamine 123 in doxorubicin- and paclitaxel-resistance cervical cancer cell lines. In addition, rucaparib significantly increased the accumulation of tritium-labeled chemotherapeutic drugs in drug resistance cervical cancer cells, and decrease the efflux of tritium-labeled chemotherapeutic drugs. Molecular docking study indicated that rucaparib could bind to the active site of the ABC transporters. The present study indicated that rucaparib could antagonize MDR in cervical cancer cells by blocking the function of ABC transporters. The results obtained in the present study provide the potential possibilities that the combination of rucaparib with other chemotherapeutic agents may benefit patients with cervical cancer.

ATP结合盒（ABC）转运蛋白的上调是导致多种类型癌症中多重耐药性（MDR）的最重要因素之一。在本研究中，我们研究了rucaparib（一种正在开发中的聚（ADP-核糖）聚合酶（PARP）抑制剂）克服宫颈癌细胞系中ABC转运蛋白介导的MDR的能力。Rucaparib显着增强了一系列常规化疗药物在耐药宫颈癌细胞株中的细胞毒作用。此外，rucaparib显着增加了对阿霉素和紫杉醇耐药的子宫颈癌细胞株中若丹明123的积累。此外，rucaparib大大增加了drug标记的化疗药物在耐药宫颈癌细胞中的蓄积，并减少of标记的化疗药物的外排。分子对接研究表明，rucaparib可以结合ABC转运蛋白的活性位点。本研究表明，rucaparib可以通过阻断ABC转运蛋白的功能来拮抗宫颈癌细胞中的MDR。本研究中获得的结果提供了rucaparib与其他化学治疗剂联合使用可能使宫颈癌患者受益的潜在可能性。