ISO-1在卵巢癌侵袭中的作用  

Effect and clinical significance of ISO-1 in the invasion of ovarian cancer

作　　者：张庆露[1] 侯桂华[1] 梁婷[1] 宋静[1] 张超[1] 

机构地区：[1]山东大学医学院实验核医学研究所,济南250012

出　　处：《山东大学学报（医学版）》2012年第9期33-39,共7页Journal of Shandong University:Health Sciences

基　　金：国家自然科学基金(81071172);中国博士后科学基金(20090461227)

摘　　要：目的探讨巨噬细胞移动抑制因子MIF特异抑制剂(S,R)-3-(4-羟苯基)-4,5-二氢-5-异噁唑乙酸甲酯(ISO-1)对卵巢癌细胞增殖、侵袭的作用以及对血管内皮生长因子受体2(vascular endothelial growth factorreceptor-2,VEGFR-2)的影响,为卵巢癌CD74靶向治疗奠定基础。方法不同浓度ISO-1作用于人卵巢癌细胞SKOV3、A2780,对照组以相应浓度的稀释液处理。MTT法检测卵巢癌细胞增殖,L-多巴色素甲酯测定M IF互变异构酶活性,微孔迁移法检测卵巢癌细胞体外侵袭,RT-PCR检测mRNA表达情况。结果 ISO-1能显著抑制人卵巢癌细胞SKOV3、A2780的增殖及其MIF互变异构酶活性(P<0.05),且两者呈正相关性(SKOV3:r=0.841,P<0.01;A2780:r=0.862,P<0.01);50μmol/L ISO-1作用于卵巢癌细胞SKOV3、A2780细胞24 h后,其穿透聚碳酸酯膜的能力显著降低(P<0.05),同时卵巢癌细胞的CD74、VEGFR-2的mRNA水平显著降低(P<0.05)。结论ISO-1通过抑制CD74的活性下调VEGF、VEGFR-2的表达,从而抑制卵巢癌细胞的增殖及侵袭。Objective To investigate the effect of the macrophage migration inhibitory factor（MIF） specific inhibitor ISO-1 [（S,R）-3-（4-hydroxyphenyl）-4,5-dihydro-5-isoxazole acetic acid methyl ester] on the proliferation and invasion of ovarian cancer cells and the expression of vascular endothelial growth factor receptor-2（VEGFR-2） mRNA,and to provide the experimental evidence for the targeted therapy of CD74 for ovarian cancer.Methods The human ovarian cancer cell lines SKOV3 and A2780 were treated with series concentrations of ISO-1,while those in the control group were treated with DMSO.MTT assay was used to measure the cell proliferation.The tautomerase activity of MIF was evaluated by using L-dopachromemethyl ester.Microporous migration assay was performed to determine the effect of ISO-1 on the invasion of SKOV3 and A2780 cells.The expression of mRNA was detected by reverse transcription polymerase chain reaction（RT-PCR）.Results ISO-1 inhibited the proliferation and the MIF tautomerase activities of SKOV3 and A2780 cells obviously（P0.05）,and the MIF tautomerase activities positively correlated with the proliferation of the ovarian cancer cells affected by ISO-1（SKOV3： r=0.841,P0.01;A2780： r=0.862,P0.01）.The number of invaded SKOV3 and A2780 cells was significantly less in the group treated by 50 μmol/L ISO-1 for 24 h than that in the control group（P0.05）.The expression of CD74、VEGFR-2 mRNA was obviously reduced after ISO-1 treatment（P0.05）.Conclusion ISO-1 can down-regulate the expression of VEGF and VEGFR-2 through inhibiting the activities of CD74,thus inhibit the proliferation and invasion of ovarian cancer cells.

关 键 词：ISO-1 卵巢癌细胞 巨噬细胞移动抑制因子 血管内皮生长因子受体-2 CD74 

分 类 号：R392.5[医药卫生—免疫学]