Epidermal growth factor enhances chemosensitivity of colon cancer by inducing cancer stem cells to enter the cell cycle

Abstract

Abstract Objective The aim of the study was to investigate whether colon cancer stem cells induced by epidermal growth factor (EGF) to enter the cell cycle enhanced the chemosensitivity of colon cancer. Methods In vitro, EGF was used to stimulate the entry of human colon cancer HCT116 cells into the cell cycle. Before and after treatment with EGF, CD133+ HCT116 cells were collected and flow cytometry was conducted to determine the apoptosis rate based on the 5-Fu and Ki-67 expression rates. The cell cycle distribution of the two groups was also determined. In vivo, a subcutaneous xenograft model of HCT116 human colon cancer cell lines in nude mice was established. The nude mice were divided into two groups and treated with EGF and 5-Fu, respectively. Differences in the growth of implanted tumors revealed the efficiency of cycle-induction combined chemotherapy. Results (1) After EGF stimulation, the S-G2/M proportion of CD133+ HCT116 cells and Ki67 expression were increased, indicating that more cancer stem cells entered the cell cycle and promoted proliferation; (2) After EGF stimulation, CD133+ HCT116 cells showed a higher apoptosis rate induced by 5-Fu. (3) Animal experiments showed that the group subjected to combined treatment with EGF and 5-Fu had smaller tumor sizes compared to the group treated with 5-Fu alone. Conclusion EGF enhanced tumor sensitivity to chemotherapeutic drugs, likely by promoting tumor stem cells to enter the cell cycle.