α-干扰素与5-FU联合作用对肝癌细胞HepG2．2．15生物学特性的影响  

Effect of IFN-α combined with 5-FU on biological characteristics of human hepatocellular carcinoma cell line HepG2.2.15

作　　者：谢风祥[1] 毛海婷[1] 李晓冰[1] 张玲[1] 顾洪涛[1] 阴海鹏[1] 周宪宾[1] 王丽[1] 李殊吏[2] 

机构地区：[1]山东省医学科学院基础医学研究所山东省医药卫生肿瘤免疫与中药免疫重点实验室山东省现代医用药物与技术重点实验室,山东济南250062 [2]山东省肿瘤医院医务部,山东济南250117

出　　处：《中华肿瘤防治杂志》2008年第7期494-498,共5页Chinese Journal of Cancer Prevention and Treatment

基　　金：山东省自然科学基金资助(Y2002C45)

摘　　要：目的:探讨α-干扰素(IFN-α)联合5-FU对肝癌细胞HepG2·2·15生物学特性的影响及其作用机制。方法:采用MTT法观察5-FU和IFN-α对HepG2·2·15细胞增殖的影响,流式细胞术检测细胞周期和细胞凋亡变化及细胞表面Fas表达变化;RT-PCR检测凋亡抑制基因Bcl-xL表达变化。结果:IFN-α单独应用对HepG2·2·15细胞增殖抑制作用较弱,与5-FU联合应用时对细胞的增殖抑制作用明显增强,P<0·01;两者联合应用对HepG2·2·15细胞周期的影响表现为与对照组和IFN-α、5-FU单用药组相比,联合用药组G0/G1期细胞比率升高(78·33%vs54·95%、60·08%和72·50%),S期比率降低(10·97%vs29·04%、18·69%和17·44%),P<0·01;经药物处理48h后,联合用药组的细胞凋亡率为(25·08±2·54)%,与对照组及IFN-α和5-FU单独应用组相比,细胞凋亡率明显增高,P<0·01。IFN-α对HepG2·2·15细胞表面Fas表达没有影响,但可协同5-FU明显提高细胞表面Fas的表达,P<0.01。联合用药组HepG2·2·15细胞Bcl-xL的表达较对照组和单药组明显下降,P<0·05。结论:IFN-α和5-FU联合应用可抑制HepG2·2·15细胞的增殖并诱导凋亡,其机制之一可能是调节凋亡抑制基因Bcl-xL的表达,影响内源性凋亡信号传导通路来发挥作用。OBJECTIVE： To explore the effect of IFN-α combined with 5-Fluorouracil （5-FU） on antitumor and apoptosis of hepataocellular carcinoma cell line HepG2. 2. 15 and their mechanism of synergistic effect. METHODS： HepG2. 2. 15 cells were treated with 5 FU in combination or not with IFN-α in vitro. Cell proliferation was evaluated by MTT assay. Cell cycle, apoptosis ratio and Fas expression on cells surface were observed by Flow cytometric assay, mRNA expression of Bcl-xL gene was measured by RT-PCR. RESUL＇IS： The inhibition effect of 5-FU plus IFN-α was significantly stronger than IFN-α alone, P〈0. 01. Compared with IFN-α group and 5-FU group, the cell percent of IFN-α plus 5-FU group was increased in G0/G1 stage（78. 33% vs 54. 95%, 60. 08% and 72.50%）, and decreased in S stage（10.97% vs 29.04%, 18. 69% and 17. 44%）, P〈0. 01. After 48 hours, the apoptosis of combined group was （ 25.08 ± 2. 54） %, which was significantly higher than that of IFN-α group and 5-FU group, P〈0. 01. IFN-α could increase the expression of Fas synergically, P〈0. 01. The expression of Bcl-xL of HepG2. 2. 15 was lower than that of control group, P〈0. 05. CONCLUSIONS： IFN-α and 5-FU could suppress the proliferation and induce apoptosis of HepG2.2. 15 cells partly by down-regulation of Bcl-xL gene level. There was an obviously synergistic effect between IFN-α and 5-FU. The mechanism of synergistic effect on promoting apoptosis of hepataocellular carcinoma cells may be related to inner signal pathwav of apoptosis.

关 键 词：干扰素Α 细胞凋亡 氟尿嘧啶 细胞周期 

分 类 号：R735.7[医药卫生—肿瘤]