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目的检测干扰素(IFNα-2b)联合5-氟尿嘧啶(5-FU)在体外对肝癌细胞株HepG2的杀伤抑制作用,并探讨可能的作用机制。方法体外复苏、培养人肝癌细胞,并单用IFNα-2b或5-FU,以及不同浓度的IFNα-2b联合5-FU对其进行干预。用MTT法测定IFNα-2b联合5-FU对体外培养的人肝癌细胞生长的抑制率;用HOECHST染色法检测药物对人肝癌细胞凋亡的影响;用免疫细胞化学法检测用药后人肝癌细胞中突变型p53、c-myc表达的变化。结果 IFNα-2b和5-FU都能抑制HepG2细胞生长,并随着作用时间的延长而增强,IFNα-2b与5-FU联合用药比单用IFNα-2b或5-FU抑制效果更明显,并随着浓度的增加和作用时间的延长而增强;IFNα-2b和5-FU均能诱导肝癌细胞凋亡,二药联用时细胞凋亡更明显,可呈剂量依赖性地诱导肝癌细胞凋亡,不同浓度下的凋亡率均明显高于对照组;IFNα-2b和5-FU均可明显抑制突变型p53、c-myc蛋白的表达,二药联用抑制作用更明显。结论IFNα-2b和5-FU联用可呈剂量和时间依赖性地抑制肝癌细胞的增殖,呈剂量依赖性地诱导肝癌细胞凋亡,下调突变型p53、c-myc蛋白的表达,表现出协同作用。这些可能是IFNα-2b和5-FU联合抗癌的部分机制。
Objective To investigate the inhibitory effect of interferon (IFNα-2b) combined with 5-fluorouracil (5-FU) on HepG2 cells in vitro and its possible mechanism. METHODS: Human hepatocellular carcinoma cells were cultured in vitro and cultured with IFNα-2b or 5-FU alone or in combination with different concentrations of IFNα-2b and 5-FU. The inhibitory rate of IFNα-2b combined with 5-FU on the growth of human hepatocellular carcinoma cells in vitro was determined by MTT assay. The effect of drugs on the apoptosis of human hepatocellular carcinoma cells was detected by HOECHST staining. The apoptosis of human hepatoma cells was detected by immunocytochemistry Mutant p53, c-myc expression changes. Results IFNα-2b and 5-FU both inhibited the growth of HepG2 cells and increased with the prolongation of time. The combination of IFNα-2b and 5-FU was more effective than IFNα-2b alone or 5-FU alone With the increase of concentration and the prolongation of action time, IFNα-2b and 5-FU can induce the apoptosis of hepatocellular carcinoma cells. When combined with the two drugs, the apoptosis was more obvious, which could induce the apoptosis of hepatoma cells in a dose- The apoptotic rate was significantly higher than that of the control group at different concentrations. Both IFNα-2b and 5-FU significantly inhibited the expression of mutant p53 and c-myc proteins. Conclusions The combination of IFNα-2b and 5-FU can inhibit the proliferation of hepatocarcinoma cells in a dose-and time-dependent manner, induce the apoptosis of hepatoma cells in a dose-dependent manner, and down-regulate the expression of mutant p53 and c-myc proteins. effect. These may be part of the mechanism of combined anti-cancer effects of IFNα-2b and 5-FU.