TY - JOUR AB - Paclitaxel in combination with carboplatin improves survival among patients with susceptible ovarian cancers, but no strategy has been established against resistant ovarian cancers. BAG3 (Bcl-2-associated athanogene 3) is one of six BAG family proteins, which are involved in such cellular processes as proliferation, migration and apoptosis. In addition, expression of BAG3 with Mcl-1, a Bcl-2 family protein, reportedly associates with resistance to chemotherapy. Our aim in this study was to evaluate the functional role of BAG3 and Mcl-1 in ovarian cancer chemoresistance and explore possible new targets for treatment. We found that combined expression of BAG3 and Mcl-1 was significantly associated with a poor prognosis in ovarian cancer patients. In vitro, BAG3 knockdown in ES2 clear ovarian cancer cells significantly increased the efficacy of paclitaxel in combination with the Mcl-1 antagonist MIM1, with or without the Bcl-2 family antagonist ABT737. Moreover, BAG3 was found to positively regulate Mcl-1 levels by binding to and inhibiting USP9X. Our data show that BAG3 and Mcl-1 are key mediators of resistance to chemotherapy in ovarian cancer. In BAG3 knockdown ES2 clear ovarian cancer cells, combination with ABT737 and MIM1 enhanced the efficacy of paclitaxel. These results suggest that inhibiting BAG3 in addition to anti-apoptotic Bcl-2 family proteins may be a useful therapeutic strategy for the treatment of chemoresistant ovarian cancers. AD - Department of Obstetrics and Gynecology, Sapporo Medical University, Sapporo 060-8543, Japan AU - Habata,Shutaro AU - Iwasaki,Masahiro AU - Sugio,Asuka AU - Suzuki,Miwa AU - Tamate,Masato AU - Satohisa,Seiro AU - Tanaka,Ryoichi AU - Saito,Tsuyoshi DA - 2016/07/01 DO - 10.3892/ijo.2016.3494 EP - 410 IS - 1 JO - Int J Oncol KW - BAG3 Mcl-1 ovarian cancer apoptosis paclitaxel chemoresistance PY - 2016 SN - 1019-6439 1791-2423 SP - 402 ST - BAG3-mediated Mcl-1 stabilization contributes to drug resistance via interaction with USP9X in ovarian cancer T2 - International Journal of Oncology TI - BAG3-mediated Mcl-1 stabilization contributes to drug resistance via interaction with USP9X in ovarian cancer UR - https://doi.org/10.3892/ijo.2016.3494 VL - 49 ER -