Long-term exposure in high viscous microenvironment facilitates acquired drug resistance of colon cancer cells to doxorubicin.

Chemotherapy is one of the most common strategies for treating colorectal cancer (CRC). However, acquired drug resistance (ADR) impairs the efficiency of chemotherapy. For CRC treatment, the long-term administration could affect cancer microenvironment and induce environment-mediated drug tolerance that contributes to ADR. Nevertheless, it is elusive that how the alteration of microenvironment affects the ADR of colon cancer cells. In this study, the effect of microenvironmental viscosity on ADR of colon cancer cells to doxorubicin (DOX) was investigated by long-term culture of colon cancer cells in different viscous media supplemented with DOX. The 50% inhibitory concentration (IC) value of drug-resistant cells established by culturing in high viscosity media was significantly higher than that of cells cultured in low viscosity media. The drug-resistant colon cancer cells established in high viscosity media exhibited higher expression levels of drug resistance-related genes (ABCC2 and ABCG2), higher migration ability and lower proliferation ability than the cells established in low viscosity medium. Long-term exposure in DOX-containing high viscosity media made the cells more tolerant to DOX and facilitated the ADR of colon cancer cells to DOX. The results disclosed the importance of microenvironmental viscosity on the ADR development and should provide useful information for cancer therapy.