Secretion of IL-6 and TGF-β2 by Colon Cancer Cells May Promote Resistance to Chemotherapy

Colon rectal cancer still stands as the third most common form of cancer worldwide. 90% of colorectal cancer failure is attributed to the development of chemoresistance. In this study, we have investigated the influence of chemokine IL-6 and growth factor TGF-β2 on dox resistance development. HT-29 (benign, Duke's stage B, colon adenocarcinoma with smad4 mutation) and Colo205 (metastatic, Duke's stage C, colon adenocarcinoma with smad4 mutation) were treated with increasing concentrations of doxorubicin for 7-days to induce resistance in the presence or absence of TGF-β2 ligand. The media after each treatment was collected and the level of secretory IL-6 was evaluated through ELISA. The media was concentrated, and isoforms of TGF-β2 were immunoprecipitated. We report that over the 7-day treatment period, an increase in IL-6 expression was observed upon treatment and the expression pattern varied based on the cancer stage. Similarly, differently expressed glycosylated forms of TGF-β2 secretion was observed with Colo205 cells while only low glycosylated form was observed in HT-29 cell line. Further analysis into the molecular mechanism could shed light on the possible role of IL-6 and TGF-β2 secretion as molecular markers for resistance development in colon cancer cells.