HCT116 cell line heterogeneity: A useful tool for preclinical research

Cancer cell heterogeneity is one of the reasons for anticancer chemotherapy failure. Nowadays, this field of research is receiving increasing attention, but mainly as a descriptive characteristic of the tumor. In this study, the property of heterogeneity of tumor colonies is considered as the basis for the identification of effective treatment schemes. A series of sequential sortings of HCT116 cells were performed based on their ability to accumulate Rhodamine 123. Subpopulations were obtained that differ significantly in their ability to accumulate the dye, including side population cells exhibiting increased chemoresistance to drugs with different mechanisms of action. The subpopulations demonstrate increased stability and retain their properties for an extended period, which makes them suitable for long-term experimental studies. The chemoresistance of side population cells is determined by the overexpression of the efflux transporter MDR1, which can be caused by rearrangement of chromosome 7. At the same time, cells that actively accumulate Rhodamine 123 also demonstrate tolerance to chemotherapeutic agents that can be the result of significant rearrangements in chromosome 21. In addition, an approach to testing of anticancer agents based on identification of effective concentrations against side population cells is proposed. Using such concentrations in the general cancer cell population will eliminate the entire tumor population, including rare and less drug-sensitive cancer stem cells, which are a reservoir for the development of a secondary tumor. The study emphasizes the importance of considering tumor heterogeneity when developing effective treatment strategies and offers practical tools to combat therapeutic resistance in cancer cells.