Ovarian cancer remains one of the most frequent causes of cancer-related death in women. Many patients with ovarian cancer suffer from de novo or acquired resistance to chemotherapy. Here, we report that RAB25 suppresses chemotherapy-induced mitochondrial apoptosis signaling in ovarian cancer cell lines and primary ovarian cancer cells. RAB25 blocks chemotherapy-induced apoptosis upstream of mitochondrial outer membrane permeabilization by either increasing antiapoptotic BCL-2 proteins or decreasing proapoptotic BCL-2 proteins. In particular, BAX expression negatively correlates with RAB25 expression in ovarian cancer cells. BH3 profiling assays corroborated that RAB25 decreases mitochondrial cell death priming. Suppressing RAB25 by means of RNAi or RFP14 inhibitory hydrocarbon-stapled peptide sensitizes ovarian cancer cells to chemotherapy as well as RAB25-mediated proliferation, invasion and migration. Our data suggest that RAB25 is a potential therapeutic target for ovarian cancer.

卵巢癌仍然是女性癌症相关死亡的最常见原因之一。许多卵巢癌患者对化疗产生新发或获得性耐药。在这里，我们报告 RAB25 在卵巢癌细胞系和原发性卵巢癌细胞中抑制化疗诱导的线粒体凋亡信号。RAB25 通过增加抗凋亡 BCL-2 蛋白或减少促凋亡 BCL-2 蛋白来阻断化疗诱导的线粒体外膜透化上游的细胞凋亡。特别是，BAX 表达与卵巢癌细胞中 RAB25 的表达呈负相关。BH3 分析证实 RAB25 减少线粒体细胞死亡启动。通过 RNAi 或 RFP14 抑制性烃钉合肽抑制 RAB25 可使卵巢癌细胞对化疗以及 RAB25 介导的增殖、侵袭和迁移敏感。我们的数据表明 RAB25 是卵巢癌的潜在治疗靶点。