Abstract: To explore the effects of fluorouracil (Fu) combined with wortmannin in wtp53/mtp53 colon cancer cells (HCT-116 and SW-480) and to clarify　the role of p53 in proliferation and apoptosis of human colon cancer cells.Methods The HCT-116 and SW-480 cells in the logarithmic growth　phase were divided into Control,Fu,Fu+wortmanin and Fu+wortmanin+PFT-α groups separately,and the cells were treated  with Fu,wortmannin and PFT-α, respectively.The survival and apoptotic rates of HCT-116 and SW-480 cells at different time (12,24， and 48 h) in various groups were detected by MTT assay and flow cytometry (FCM) with Annexin V-FITC individually.Results Compared with Fu group,the survival rates of HCT-116 and SW-480 cells in Fu+wortmannin group were significantly decreased with a time-dependent decrease (P<0.05);FCM analysis showed that the apoptotic rates of HCT-116 and SW-480 cells were increased with the prolongation of time (P<0.05);compared with  Fu+wortmannin group,the  survival rate　of SW-480 cells  in Fu+wortmannin+PFT-α group at 48 h was significantly decreased(P<0.05),and the apoptotic rate was markedly increased(P<0.05),while the apoptotic and survival rates of HCT-116  cells had nosignificant change(P>0.05).Conclusion Wortmannin could enhance the inhibitory effect of Fu on the human colon cells (HCT-116 and SW-480);inhibition of p53 expression can enhance the inhibitory effect  of Fu combined with  wortmannin  on proliferation of mtp53 SW-480 cells and promote the apoptosis of mtp53 SW-480 cells.

Key words: fluorouracil, wortmannin, p53, apoptosis, colon neoplasms