Reduction of G0 phase cells of colon cancer caco-2 cells may enhance 5-fluorouracil efficacy

Objective:A major problem in the chemotherapy of colon caner may be due to those cells that are in residence in the G 0 phase where they are less vulnerable to conventional therapy.To overcome this phenomenon, we attempted to recruit the reentry of these cells into the cell cycle via a signaling pathway that manipulates tumor growth.Methods:Epidermal growth factor(EGF)was used to stimulate colon cancer caco-2 cells.FACS analysis and proliferating cell nuclear antigen(PCNA)staining were used to estimate the cell cycle transition and cell proliferation activated by EGF,and a MTT assay was used to evaluate the synergistic effect of EGF and chemotherapy.Results:The percentage of caco-2 cells in the G 0 /G 1 phase was significantly reduced by nearly 20%and the percentages in the S and G 2 /M phases were increased by EGF.The combined use of EGF and 5-fluorouracil(5-FU)enhanced the caco-2 cell chemosensitivity to 5-FU,reaching a maximum of an approximately threefold greater sensitivity than to 5-FU alone as judged by the 50%inhibiting concentration(IC 50 ). Conclusion:Our study demonstrated that stimulation by EGF enhanced the chemosensitivity of caco-2 cells to 5-FU,which may be a novel therapeutic protocol in colon cancer.