title: Low-dose cisplatin-induced CXCR4 expression promotes proliferation of ovarian cancer stem-like cells.
abstract: Chemoresistance blocks the efficient treatment of epithelial ovarian cancer, which is the most lethal of all gynecological cancers. Cancer stem cells are believed to be at least partially responsible for the development of chemoresistance. In this study, the effect of cisplatin (CDP) on the enrichment and proliferation of cancer stem-like cells (CSLCs) was investigated, and the underlying mechanisms of action were elucidated. An in vitro anchor-free system was employed to enrich CSLCs from the SKOV3 human epithelial ovarian cancer cell line. Our results showed that treatment with low concentrations of CDP resulted in better-enriched CSLCs, with higher proliferative activities. Low dose of CDP was found to induce the expression of chemokine (C-X-C motif) receptor 4 (CXCR4), which is an important stemness marker in cancer stem cells as well as a promising therapeutic target for ovarian cancer treatment. Results also showed that overexpressed CXCR4 generated chemoresistance. Based on these results, it may be concluded that, at low concentrations, CDP itself contributes to the development of drug resistance. This finding provides novel insight into the mechanisms underlying chemoresistance and has significant therapeutic implications for epithelial ovarian cancer treatment.
authors.affiliation: The International Peace Maternity and Child Health Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai 200030, China.
authors.forename: Yifei
authors.initials: Y
authors.lastname: Chen
authors.affiliation: The International Peace Maternity and Child Health Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai 200030, China.
authors.forename: Shuying
authors.initials: S
authors.lastname: Wang
authors.affiliation: The International Peace Maternity and Child Health Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai 200030, China.
authors.forename: Shixia
authors.initials: S
authors.lastname: Bu
authors.affiliation: The International Peace Maternity and Child Health Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai 200030, China.
authors.forename: Minhua
authors.initials: M
authors.lastname: Xu
authors.affiliation: The International Peace Maternity and Child Health Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai 200030, China laidongmei@hotmail.com.
authors.forename: Dongmei
authors.initials: D
authors.lastname: Lai
mesh_terms: D014408:Biomarkers, Tumor / Q000378:metabolism; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects*; D002945:Cisplatin / Q000008:administration & dosage*; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D014411:Neoplastic Stem Cells / Q000473:pathology*; D010051:Ovarian Neoplasms / Q000473:pathology*; D019718:Receptors, CXCR4 / Q000378:metabolism*
chemical_list: D014408:Biomarkers, Tumor; C527276:CXCR4 protein, human; D019718:Receptors, CXCR4; D002945:Cisplatin
keywords: CXCR4; cancer stem cell; chemoresistance; human epithelial ovarian cancer
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