Acquired Multicellular- and Extra Cellular Matrix- mediated Resistance in a Three-dimensional Model of HT-29 Cancer Cells

Here we established a three-dimensional (3D) model for HT-29 colorectal cancer cells using type I collagen as scaffolds and further evaluated the difference of cells through the 3D model and through monolayer culture (2D) with regards to their morphology and drug sensitivity. A couple of morphological differences were observed between the above two types of cancer cell. The cells by the 3D model could aggregate to form cellular spheroids and even produced microvilli on their surface whereas the cells by the 2D adhered to plate and lost their original shape. In addition, viabilities of both cells were observed to decrease upon exposure to butyric acid (BA) at various concentrations (2 similar to 40 mM) for 12, 24, 48 and 72 h, but the cell survival rates by 3D were significantly higher than those by 2D at the same drug concentrations. Also after BA treatment their cell apoptosis was investigated. Our flow cytometric analysis indicated that the cell apoptosis by 2D was extremely low at early stage but had high rates of apoptotic and necrotic and a clear dose-dependent relationship but for the cells by 3D was completely opposite to the result of the cells by 2D. In summary, our findings further demonstrated that the HT-29 colon cancer cells by the 3D showed a significant drug resistance in comparison to the cells by the 2D. Therefore, our research result showed that the 3D model can provide an effective in-vitro method to screen drugs for colon cancer treatment.