title: Rab25 is responsible for phosphoinositide 3-kinase/AKT‑mediated cisplatin resistance in human epithelial ovarian cancer cells.
abstract: Rab25, a member of the Rab family of small guanosine triphosphatase, was reported to have an essential role in the development of human epithelial ovarian cancer. The present study demonstrated that Rab25 mediated the sensitivity of ovarian cancer to cisplatin, a first‑line chemotherapeutic agent for the treatment of ovarian cancer in the clinic. Overexpression of Rab25 and increased phosphoinositide 3‑kinase (PI3K)/AKT signaling were detected in cisplatin‑resistant SKOV‑3 cells compared with those in cisplatin‑sensitive ES‑2 cells. The results of the present study indicated that cisplatin resistance was primarily due to reduced G1 cell cycle arrest following cisplatin treatment in SKOV‑3 cells. By contrast, the corresponding phenomenon was not observed following treatment with a Rab25‑specific small interfering RNA or treatment with the PI3K/AKT inhibitor LY294002. Of note, inhibition of the PI3K/AKT pathway reduced Rab25 gene expression and sensitized SKOV‑3 cells to cisplatin. Furthermore, knockdown of Rab25 showed an effect comparable with blocking the PI3K/AKT pathway. In conclusion, the results of the present study demonstrated that PI3K/AKT and Rab25 significantly contributed to cisplatin resistance in human epithelial ovarian cancer; in addition, silencing Rab25 or inhibiting the PI3K/AKT pathway markedly increased the sensitivity of these cells to cisplatin.
authors.affiliation: Department of Obstetrics and Gynecology, Ningxia People's Hospital, Yinchuan, Ningxia 750000, P.R. China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Fan
authors.affiliation: Department of Stomatology, Ningxia Medical University, Yinchuan, Ningxia 750004, P.R. China.
authors.forename: Long
authors.initials: L
authors.lastname: Wang
authors.affiliation: Department of Obstetrics and Gynecology, Ningxia People's Hospital, Yinchuan, Ningxia 750000, P.R. China.
authors.forename: Xuechuan
authors.initials: X
authors.lastname: Han
authors.affiliation: Department of Obstetrics and Gynecology, Ningxia People's Hospital, Yinchuan, Ningxia 750000, P.R. China.
authors.forename: Xueqin
authors.initials: X
authors.lastname: Liu
authors.affiliation: Department of Obstetrics and Gynecology, Ningxia People's Hospital, Yinchuan, Ningxia 750000, P.R. China.
authors.forename: Hongyun
authors.initials: H
authors.lastname: Ma
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects / Q000235:genetics; D000077216:Carcinoma, Ovarian Epithelial; D045744:Cell Line, Tumor; D002945:Cisplatin / Q000494:pharmacology; D019008:Drug Resistance, Neoplasm / Q000235:genetics*; D005260:Female; D059585:G1 Phase Cell Cycle Checkpoints / Q000187:drug effects; D015870:Gene Expression; D055785:Gene Knockdown Techniques; D006801:Humans; D009375:Neoplasms, Glandular and Epithelial / Q000235:genetics* / Q000378:metabolism*; D010051:Ovarian Neoplasms / Q000235:genetics* / Q000378:metabolism*; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D034741:RNA, Small Interfering / Q000235:genetics; D015398:Signal Transduction / Q000187:drug effects; D020691:rab GTP-Binding Proteins / Q000235:genetics*
chemical_list: D000970:Antineoplastic Agents; D034741:RNA, Small Interfering; C509763:Rab25 protein, human; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt; D020691:rab GTP-Binding Proteins; D002945:Cisplatin