Observation of ovarian cancer stem cell behavior and investigation of potential mechanisms of drug resistance in three-dimensional cell culture

• Published in: Journal of bioscience and bioengineering 2014-08, Vol.118 (2), p.214-222
• Main Authors: Chen, Junsong, Wang, Jing, Zhang, Yunxia, Chen, Dengyu, Yang, Cuiping, Kai, Cai, Wang, Xiaoying, Shi, Fangfang, Dou, Jun
• Format: Article
• Language: English
• Subjects: Animals; Antineoplastic Agents - pharmacology; Apoptosis; Biological and medical sciences; Biotechnology; Cancer stem cells; Carboplatin - pharmacology; Carcinogenesis - pathology; Carcinoma, Ovarian Epithelial; Cell Culture Techniques; Cell Line, Tumor; Cell Shape; Cell Survival - drug effects; Chemoresistance; Cisplatin - pharmacology; Drug Resistance, Neoplasm; Drug Screening Assays, Antitumor; Epithelial ovarian cancer; Female; Fluorouracil - pharmacology; Fundamental and applied biological sciences. Psychology; Humans; Mice, Inbred BALB C; Mice, Nude; Neoplasm Transplantation; Neoplasms, Glandular and Epithelial - drug therapy; Neoplastic Stem Cells - drug effects; Neoplastic Stem Cells - physiology; Ovarian Neoplasms - drug therapy; Three-dimensional culture; Two-dimensional culture
• ISSN: 1389-1723; 1347-4421
• DOI: 10.1016/j.jbiosc.2014.01.008

Cancer cells behave differently in a three-dimensional (3D) cell culture compared with in the conventional two-dimensional (2D) one. Accumulated evidences indicate that the characteristics of cancer stem cells (CSCs) are different from common cancer cells due to their ability to produce tumors and resist chemoradiation. The objective of this work was to observe CSC behavior and investigate the potential mechanisms of CSC drug resistance in 3D versus 2D in vitro environment. We first demonstrated that the CD44+CD117+cells isolated from the human epithelial ovarian cancer HO8910 cell line have the properties of CSCs that revealed faster growth, larger tumorsphere and stronger survival potential in the hypoxic environment in 3D cell culture as well as more powerful tumorigenicity in a xenograft mice than the HO8910 cells. The CD44+CD117+CSCs also exhibited high chemoresistance to anticancer drugs when the cells were incubated with 5-fluorouracil, cisplatin and carboplatin, respectively in 3D versus 2D environment. This might be associated with the high expression of ABCG2, ABCB1 and the high expression of MMP-2 and MMP-9 in CD44+CD117+CSCs. Overall, these results suggest the advantages of using 3D culture model to accurately display CSC behavior in vitro. 3D model may improve the efficacy of screening anticancer drugs for treatment of ovarian CSCs. •We demonstrate the HO8910 CD44+CD117+cells posses EOC CSC characteristics.•Using 3D culture model could accurately display EOC CSC behavior in vitro.•CD44+CD117+CSCs exhibit high chemoresistant to 5Fu, cisplatin in 3D versus 2D culture.•EOC CSC high chemoresistance are associated with high expression of ABCG2 and MMP-2.•3D model improves the efficacy of screening anticancer drugs for treatment of EOC CSCs.