血红素加氧酶对肝癌耐药细胞株Bel/Fu化疗敏感性的影响  

Effect of heme oxygenase on chemosensitivity of drug-resistant hepatic carcinoma Bel/Fu cell line

作　　者：张隽开[1] 王忠裕[1] 丁大朋[1] 辛毅[1] 

机构地区：[1]大连医科大学附属第一医院普外科,辽宁大连116044

出　　处：《中华肿瘤防治杂志》2009年第13期990-993,共4页Chinese Journal of Cancer Prevention and Treatment

摘　　要：目的:评估血红素加氧酶(HO)对肝癌耐药细胞化疗敏感性的影响,探讨HO对肝癌细胞多药耐药性可能的影响机制。方法:血红素加氧酶抑制剂锌卟啉(ZnPP)和诱导剂Hemin作用于Bel/Fu肝癌耐药细胞株,分别应用MTT、RT-PCR和流式细胞术检测细胞株对化疗药物敏感性、血红素加氧酶-1(HO-1)及多药耐药基因(MDR-1)核酸水平表达量与P-糖蛋白(P-GP)功能。结果:Hemin作用于Bel/Fu细胞诱导24 h后,化疗药物半数抑制浓度明显增加(P<0.01),HO-1 mRNA表达明显增加(F=71.513,P<0.05),MDR-1 mRNA的表达量显著增加(F=2 340,P<0.01),且呈剂量依赖趋势,ZnPP干预组表现则相反;MDR-1cDNA/β-actin的表达量呈现与HO-1cDNA/β-actin平行变化的趋势,两者呈直线正相关(r=0.992,a=-0.044,b=1.223);Hemin组罗丹明荧光曲线明显左移,且浓度越高曲线左移越明显,而ZnPP组则表现为曲线右移,出现相反的结果。结论:影响HO-1的表达可改变肝癌耐药细胞株的化疗敏感性,这种变化是通过影响MDR-1表达,改变P-GP药物外排功能实现的;HO-1可作为逆转肿瘤多药耐药的潜在作用靶点。OBJECTIVE： To study the effect and mechanism of heme oxygenase （HO） on chemosensitivity of drugresistant hepatic carcinoma Bel/Fu cell line. METHODS： The drug sensitivity test of Bel/Fu was performed with MTT assay. HO-1mRNA and MDR-1mRNA levels were determined by RT PCR technique. Rhodamine123 retention fluorescent intensity measured by flow cytometry was used to detect the function of P-GP. RESULTS： After Bel/Fu cells being dealt with Hemin for 24 h, there were significant differences in 50% inhibiting concentration （IC50） of chemical drugs between the control groups and contrast group （P〈0. 01）. The mRNA expression of HO-1 and MDR-1 in the cells of the control group were significantly higher than those in the contrast group （F=71. 513, P〈0.05;F=2 340, P〈0.01）, of which were both consistent with the dose effect curve. The curve of rhodamine123 retention fluorescent intensity in the control cells removed left award from the place of the contrast group, which indicated that the efflux pump function of P-GP was strengthened. The control groups by ZnPP, however, showed a contrary result. Lineal correlation analysis showed that the HO-1 mRNA levels were significantly correlated with those of MDR-1 （r=0.992, a=-0.044, b=1.223）. CONCLUSIONS： Inpacting heine oxygenas 1 can influence the chemosensitivity of Bel/Fu cell line, which relates with its action in up（or down）-regulation of MDR-1 expression and efflux pump function of P-GP. The enzyme of HO-1 may be a new target of reversing multidrug resistance in liver cancer cells.

关 键 词：肝肿瘤 多药耐药相关蛋白质类 血红素加氧酶-1 抗药性 肿瘤 

分 类 号：R735.7[医药卫生—肿瘤]