丙酮酸乙酯对人胰腺癌细胞的抑制作用

Inhibitory effect of ethyl pyruvate on the human pancreatic carcinoma cell line

目的观察丙酮酸乙酯(ethyl pyruvate,EP)对人胰腺癌细胞PANC-1和AsPC-1增殖、凋亡及高迁移率族蛋白B1(high mobility group protein B1,HMGB1)mRNA表达水平的影响。方法采用MTT和FCM法分别检测EP与5-氟尿嘧啶(5-fluorouracil,5-FU)单独及联合作用(EP组,E组;5-FU组,F组;联合组,EF组)对PANC-1和AsPC-1细胞增殖和凋亡的作用;通过Real Time-PCR(RT-PCR)观察各用药组对PANC-1和AsPC-1细胞HMGB1mRNA表达水平的影响。结果随着药物浓度的增加,各用药组细胞增殖活性及HMGB1mRNA表达水平逐渐降低,凋亡率逐渐增高。E0.5225F10、E1.0450F20、E2.0900F40、E3.1350F80组的胰腺癌细胞抑制率均比相应E组高(P<0.05),EF组的胰腺癌细胞凋亡率均比相应E组高(P<0.05),E3.1350F80、E4.1800F160组均比相应E组的胰腺癌细胞HMGB1mRNA表达水平高(P<0.05)。结论 EP可能通过对HMGB1表达的影响,抑制胰腺癌细胞增殖和诱导细胞凋亡,从而起到抗胰腺癌作用,但是其具体机制及在体内的作用有待进一步深入研究。

Objective To investigate the influence of ethyl pyruvate（EP） on proliferation and apoptosis of human pancreatic carcinoma PANC-1 and AsPC-1 cells and expression of high mobility group protein B1（HMGB1） mRNA.Methods The effects of EP and 5-FU alone and EP combined with 5-FU（EP group,E group;5-FU group,F group;EP combined with 5-FU group,EF group）on the proliferation and apoptosis of PANC-1 and AsPC-1 cells were measured by MTT and FCM,respectively.HMGB1 mRNA expression level in PANC-1and AsPC-1 cells in each medication group was determined by real-time PCR（RT-PCR）.Results With the drug level gradually increasing,proliferation and HMGB1 mRNA expression level of pancreatic cancer cells were gradually decreased and the cell apoptosis ratio was gradually increased in each medication group.Inhibitory ratios of pancreatic carcinoma cells were all higher after being treated with E0.5225F10,E1.0450F20,E2.0900F40 and E3.1350F80,compared with the controlled E groups（P〈0.05）.Apoptosis ratios of pancreatic cancer cells in EF groups were all raised compared with their controlled E groups（P〈0.05）.Expression levels of HMGB1 mRNA were all degraded after being treated with E3.1350F80/E4.1800F160 compared with the controlled E groups（P〈0.05）.Conclusion EP could inhibit cell proliferation and induce cell apoptosis by inhibiting HMGB1 expression in pancreatic carcinoma cells.Thus,EP has an effect of anti-pancreatic carcinoma,and further research is needed on its detailed mechanism and effect in vivo.