Effect And Mechanism Of Genistein On Proliferation,apoptosis And Chemotherapy Sensitivity In Human Colorectal Carcinoma Cell Line

Objective: To investing the role of Genistein on the proliferation and apoptosis of the human colorectal carcinoma cell line HCT-116, also to explore the mechanisms of the Survivin and Notch1 gene in the process of apoptosis. To study the effect and its possible mechanisms of Genistein combined with 5-FU on chemotherapy sensitivity in the human colorectal carcinoma cell line HCT-116.Methods: In vitro, human colorectal carcinoma cell line HCT-116 was treated by Genistein and(or) 5-FU in various concentrations respectively alone or incombination, and the effect of cell growth inhibition was analyzed by MTT assay; cell cycle and apoptosis rate was examined by flow-cytometry(FCM). RT-PCR and immunohistochemistry s-p method was used to observe the expression of Survivin/Notch1.Results: Genistein could inhibit the growth of the human colorectal cancer cell line HCT-116. The inhibitory effect was does-and-time dependent (P<0.05 or P<0.01). Compared with Genistein or 5-FU individual drug group, Genistein combined with 5-FU significantly inhibited the growth of HCT-116 cell(P<0.01). Flow-cytometry test results showed:Genistein and(or) 5-FU could induce HCT-116 cell apoptosist after treated with for 48h and the ratio of S phase increase(P<0.01), Compared to Genistein or 5-FU individual drug group, Genistein combined with 5-FU significantly induced apoptosis of HCT-116 cells and S phase cell increase distinctly in the combine group(P<0.01). RT-PCR and immunohistochemistry s-p method show the expression of Survivin/Notch1 decreased after treated with Genistein in various concentrations(p<0.05), compared to control group, 5-FU increased the expression of mRNA and protein of survivin in HCT-116 cells(p<0.05), while Genistein combined with 5-FU could decreased the over-expression of survivin induce by 5-FU(p<0.05).Conclusion: Genistein can strongly inhibit the growth and induce the apoptosis of human colorectal cancer cell line in a does-and-time dependent manner, Genistein combined with 5-FU could significantly increase the anti-colorectal cancer effect. It may be its mechanisms inducing apoptosis by down- regulation of Survivin and Notch-1 expression. Genistein can inhibit the over-expression of survivin induced by 5-FU in HCT-116 cell. This may be one of the key mechanisms by which genistein sensitize HCT-116 cell to 5-FU.