阿苯达唑对耐药卵巢癌细胞糖酵解的影响

目的探讨阿苯达唑(albendazole,ABZ)对人耐顺铂卵巢癌SKOV-3/DDP细胞糖酵解的影响。方法通过溴化二甲噻唑二苯四氨唑(MTT)比色法检测ABZ对卵巢癌SKOV-3/DDP细胞体外增殖的影响,求得抑制率分别为0%、25%、50%、75%时所对应的ABZ的浓度,实验分为对照组、IC25组、IC50组和IC75组,每组给予相应浓度的ABZ处理,并且按照ABZ作用时间再将每组分为12、24、36 h亚组。按照分组,在设定的时间点,分别用比色法测定己糖激酶(hexokinase,HK)和丙酮酸激酶(pyruvate kinase,PK)活性,用酶标仪法测定乳酸脱氢酶(lactate dehydrogenase,LDH)的活性,用RT-PCR法测定Akt mRNA和Myc mRNA的表达。结果经过不同浓度的ABZ处理SKOV-3/DDP细胞发现,ABZ能抑制SKOV-3/DDP细胞体外生长(P<0.05),呈剂量依赖性,抑制率为0%所对应的ABZ浓度为0μmol/L,抑制率25%的浓度(IC25)为(1.43±0.21)μmol/L,抑制率50%的浓度(IC50)为(8.64±0.74)μmol/L,抑制率75%的浓度(IC75)为(52.48±3.99)μmol/L。与对照组相比,经过ABZ处理的SKOV-3/DDP细胞的HK、PK、LDH活性明显降低(P<0.05),且Akt基因和Myc基因的表达下调(P<0.05)。结论 ABZ能够抑制SKOV-3/DDP细胞糖酵解酶活性,并能下调糖酵解相关基因的表达。

Effect of albendazole on glycolysis of cisplatin-resistant ovarian cancer cells

Objective To study the effect of albendazole（ABZ） on glycolysis of human cisplatin-resistant ovarian cancer SKOV3/DDP cells.Methods Proliferation of SKOV3/DDP cells was detected by methyl thiazolyl tetrazolium（MTT） colorimetry after treatment with ABZ in vitro.SKOV3/DDP cells were divided into control group,IC₂5 group,IC₅0 group,and IC₇5 group according to the concentration of ABZ with an inhibition rate of 0%,25%,50%,and 75%.Each group was further divided into 12,24 and 36 h subgroups according to the action time of ABZ at a certain concentration.Activities of hexokinase（HK）,pyruvate kinase（PK） and lactate dehydrogenase（LDH） were detected by colorimetry and ELISA,respectively,and expression of Akt mRNA and Myc mRNA was detected by RT-PCR at the setting time points.Results ABZ inhibited the proliferation of SKOV3/DDP cells in a dose-dependent manner（P<0.05） with an inhibition rate of 0%,25%,50% and 75% at the concentration of 0,1.43±0.21,8.64±0.74 and 52.48±3.99 μmol/L,respectively,in control group,IC₂5 group,IC₅0 group and IC₇5 group.The activities of LDH,HK,PK and the expression levels of Akt mRNA and Myc mRNA were significantly lower in IC₂5 group,IC₅0 group and IC₇5 group than in control group（P<0.05）.Conclusion ABZ can inhibit the activities of glycolytic enzymes and down-regulate the expression of glycolysis-related genes in vitro.