ISO-1对大肠癌细胞增殖的影响

The Effects of ISO-1 on the Proliferation of the Colorectal Cancer Cell Lines

目的研究选择性MIF互变异构酶活性抑制剂ISO-1对大肠癌细胞增殖的影响并探讨其可能机制。方法不同浓度的ISO-1（0.01-100μmol/L）作用于人大肠癌细胞Lovo、SW116和鼠大肠癌细胞CT26,对照组以相应浓度的DMSO处理。MTT法观察ISO-1对大肠癌细胞增殖的影响。通过L-多巴色素甲酯测定MIF互变异构酶活性。ELISA法测定ISO-1作用后大肠癌细胞MIF蛋白水平。RT-PCR检测ISO-1作用后大肠癌细胞IL-8 mR-NA的表达。结果ISO-1抑制了Lovo细胞的增殖,且呈剂量和时间依赖性;ISO-1同样抑制了SW116（F=800.694,P〈0.01）和CT26细胞的增殖（F=879.544,P〈0.01）。ISO-1抑制了Lovo和SW116细胞内MIF互变异构酶活性,并且与抑制大肠癌细胞增殖程度呈正相关性（Lovo：r=0.54,P=0.005;SW116：r=0.683,P〈0.01）;ISO-1降低了Lovo和SW116细胞IL-8 mRNA表达水平（Lovo：0.1541±0.0.019 vs.0.2081±0.030,P〈0.05;SW116：0.1509±0.017vs.0.2354±0.01.P〈0.05）。结论ISO-1不仅抑制人大肠癌细胞Lovo和SW116的增殖,而且也抑制鼠大肠癌细胞CT26的增殖,其可能机制为ISO-1抑制了MIF的互变异构酶活性并下调IL-8的表达。

Objective To investigate the effects of ISO-1,a selective MIF tautomerase activity inhibitor,on the proliferation of the colorectal cancer cell lines and its probable mechanisms.Methods The human colorectal cancer cell lines Lovo,SW116 and the mice colorectal cancer cell lines CT26,were treated with series concentrations of ISO-1（0.01mol/L to 100μmol/L）,while those in the control group were treated with the corresponding concentration of dimethylsulfoxide（DMSO）.MTT assay was used to evaluate the inhibition ratios.The tautomerase activity of MIF was measured using L-dopachrome methyl ester.MIF protein levels were determined using ELISA.And the expression of IL-8 mRNA was detected by reverse transcription polymerase chain reaction（RT-PCR）.Results ISO-1 inhibited the proliferation of Lovo cells in a time-and-concentration-dependent manner,and ISO-1 also inhibited the proliferation of SW116 cells and CT26 cells.The MIF tautomerase activities were significantly inhibited after ISO-1 treatment,and positively correlated with the proliferation of the colorectal cancer cell lines affected by ISO-1（Lovo： r=0.54,P=0.005;SW116： r=0.683,P〈0.01）.The expression of IL-8 mRNA was obviously reduced after ISO-1 treatment.（Lovo： 0.1541±0.019 vs 0.2081±0.030,P〈0.05;SW116： 0.1509±0.017vs.0.02354±0.01,P〈0.05）.Conclusion ISO-1 can not only inhibit the proliferation of the human colorectal cancer cell lines Lovo,SW116 but also inhibit the proliferation of the mice colorectal cancer cell lines.The mechanism may be involved in the inhibition of the tautomerase activities of MIF and the down-regulation of IL-8 levels.