Reduction of G_0 phase cells of colon cancer caco-2 cells may enhance 5-fluorouracil efficacy

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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. 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 three fold greater sensitivity than t 5: FU alone as judged by the 50% inhibiting concentration (IC50). 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 .
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