Abstract

Shuying Wang^†,

Shixia Bu,

Minhua Xu and

Dongmei Lai^*

^† These authors contributed equally to this work.

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.

Keywords   human epithelial ovarian cancer; chemoresistance; cancer stem cell; CXCR4

Received   2015-9-25　　

Accepted  2015-11-12

Funding  This work was supported by the grants from the National Natural Science Foundation of China (Nos. 81401216 and 81200471), the Shanghai Municipal Health & Family Planning Commission (No. 20134Y128), the Shanghai Jiaotong University School of Medicine (No.

* Correspondence address  Tel/Fax: +86-21-64070434-27701; E-mail: [email protected]