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http://dx.doi.org/10.5352/JLS.2016.26.11.1313

Comparative Evaluation of Colon Cancer Stemness and Chemoresistance in Optimally Constituted HCT-8 cell-based Spheroids  

Lee, Seung Joon (Laboratory of Mucosal Exposome and Biomodulation, Department of Biomedical Sciences, Pusan National University School of Medicine)
Kim, Hyoung-Kab (Department of Environmental Engineering, Gyungnam National University of Science and Technology)
Lee, Hyang Burm (Division of Food Technology, Biotechnology and Agrochemistry, Chonnam National University)
Moon, Yuseok (Laboratory of Mucosal Exposome and Biomodulation, Department of Biomedical Sciences, Pusan National University School of Medicine)
Publication Information
Journal of Life Science / v.26, no.11, 2016 , pp. 1313-1319 More about this Journal
Abstract
Cancer is a complex disease heterogeneously composed of various types of cells including cancer stem-like cells responsible for relapse and chemoresistance in the tumor microenvironment. The conventional two-dimensional cell culture-based platform has critical limitations for representing the heterogeneity of cancer cells in the three-dimensional tumor niche in vivo. To overcome this insufficiency, three-dimensional cell culture methods in a scaffold-dependent or -free physical environment have been developed. In this study, we improved and simplified the HCT-8 colon cancer cell-based spheroid culture protocol and evaluated the relationship between cancer stemness and responses of chemosensitivity to 5- Fluorouracil (5-FU), a representative anticancer agent against colon cancer. Supplementation with defined growth factors in the medium and the culture dish of the regular surface with low attachment were required for the formation of constant-sized spheroids containing $CD44^+$ and $CD133^+$ colon cancer stem cells. The chemo-sensitivities of $CD44^+$ cancer stem cells in the spheroids were much lower than those of $CD44^-$ non-stem-like cancer cells, indicating that the chemoresistance to 5-FU is due to the stemness of colon cancer cells. Taken together, the inflammation and oncogenic gut environment-sensitive HCT-8 cell-based colon cancer spheroid culture and comparative evaluation using the simplified model would be an efficient and applicable way to estimate colon cancer stemness and pharmaceutical response to anticancer drugs in the realistic tumor niche.
Keywords
Cancer stem cell; chemoresistance; colon cancer; 5-Fluorouracil (5-FU); spheroid;
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