title: Cancer-associated fibroblasts attenuate Cisplatin-induced apoptosis in ovarian cancer cells by promoting STAT3 signaling.
abstract: One of the main reasons for treatment failure in ovarian cancer is acquired drug resistance. Cancer associated fibroblasts (CAFs) are known to enhance chemoresistance in many human tumors. However, its contributions to chemoresistance acquisition in ovarian cancer are not well understood. Here, we provide the first evidence that the conditioned medium of CAFs (CAFs-CM) could attenuate the sensitivity to Cisplatin in A2780 and ES2 ovarian cancer cells and protect them from Cisplatin-induced apoptosis. We found the expression level of two anti-apoptotic proteins, Bcl-2 and Survivin, as well as their upstream controller p-STAT3 were significantly increased when ovarian cancer cells were exposed to CAFs-CM. Furthermore, inhibition of STAT3 signaling with Cryptotanshinone could down-regulate the expression of Bcl-2 and Survivin, thus weaken the post-target resistance to Cispaltin mediating by CAFs-CM in ovarian cancer cells. In conclusion, our data suggested that CAFs could activate the anti-apoptotic STAT3 signaling, thereby decrease the Cisplatin-induced apoptosis and promote chemoresistance in ovarian cancer.
authors.affiliation: Department of Obstetrics and Gynecology, RenJi Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai Key Laboratory of Gynecologic Oncology, Shanghai, China.
authors.forename: Huan
authors.initials: H
authors.lastname: Yan
authors.affiliation: Department of Obstetrics and Gynecology, RenJi Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai Key Laboratory of Gynecologic Oncology, Shanghai, China.
authors.forename: Bi-Ying
authors.initials: BY
authors.lastname: Guo
authors.affiliation: Department of Obstetrics and Gynecology, RenJi Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai Key Laboratory of Gynecologic Oncology, Shanghai, China. Electronic address: drzhangshu@126.com.
authors.forename: Shu
authors.initials: S
authors.lastname: Zhang
mesh_terms: D000970:Antineoplastic Agents / Q000008:administration & dosage; D017209:Apoptosis / Q000187:drug effects*; D002450:Cell Communication / Q000187:drug effects; D045744:Cell Line, Tumor; D002945:Cisplatin / Q000008:administration & dosage*; D004305:Dose-Response Relationship, Drug; D019008:Drug Resistance, Neoplasm; D005260:Female; D005347:Fibroblasts / Q000473:pathology*; D006801:Humans; D010051:Ovarian Neoplasms / Q000188:drug therapy* / Q000378:metabolism* / Q000473:pathology; D050796:STAT3 Transcription Factor / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects; D015854:Up-Regulation / Q000187:drug effects
chemical_list: D000970:Antineoplastic Agents; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human; D002945:Cisplatin
keywords: Apoptosis; Cancer-associated fibroblasts; Chemoresistance; Epithelial ovarian cancer; STAT3