氟尿嘧啶联合渥曼青霉素对人结肠癌细胞增殖和凋亡的影响

目的：探讨氟尿嘧啶(Fu)联合渥曼青霉素(wortmannin)对人野生型及突变型p53结肠癌细胞株（HCT-116和SW-480）增殖和凋亡的影响，阐明p53对人结肠癌细胞增殖和凋亡的作用。方法：将处于对数生长期的 HCT-116和SW-480人结肠癌细胞株分为空白对照组、氟尿嘧啶组、氟尿嘧啶联合渥曼青霉素组和氟尿嘧啶联合渥曼青霉素及p53抑制剂（PFT-α）组，分别给予氟尿嘧啶、渥曼青霉素及PFT-α，采用噻唑盐比色法(MTT)、Annexin V-FITC流式细胞术（FCM）检测各组细胞12、24和48 h的存活率和细胞凋亡率。结果：与氟尿嘧啶组比较，渥曼青霉素联合氟尿嘧啶组HCT-116和SW-480细胞存活率显著降低（P<0.05），并随时间延长而逐渐降低；流式细胞术（FCM）检测，各组细胞凋亡率随时间的延长而增高（P<0.05）；与渥曼青霉素联合氟尿嘧啶组比较，氟尿嘧啶联合渥曼青霉素及PFT-α组HCT-116细胞存活率及细胞凋亡率无明显变化（P>0.05），而SW-480细胞48 h的存活率显著降低（P<0.05），凋亡率显著增高（P<0.05）。结论：渥曼青霉素能显著增强氟尿嘧啶对人结肠癌细胞增殖的抑制作用并促进结肠癌细胞凋亡；抑制p53表达能进一步增强渥曼青霉素联合氟尿嘧啶对p53突变型SW-480细胞增殖的抑制作用并促进细胞凋亡。
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Effects of fluorouracil combined with wortmannin on proliferation and apoptosis in human colon cancer cells

Objective 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 no significant 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.