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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 macrophage migration inhibitory factor MIF-specific inhibitor (S, R) -3- (4-hydroxyphenyl) -4,5-dihydro- Proliferation and invasion of cancer cells, as well as the effects on vascular endothelial growth factor receptor-2 (VEGFR-2), and lay a foundation for the targeted therapy of CD74 in ovarian cancer. Methods The human ovarian cancer cells SKOV3 and A2780 were treated with different concentrations of ISO-1, and the control group was treated with the corresponding dilutions. MTT assay was used to detect the proliferation of ovarian cancer cells, the activity of MIF tautomerase was detected by L-dopachrome methyl ester assay, the invasion of ovarian cancer cells was detected by micropore migration method, and the mRNA expression was detected by RT-PCR. Results ISO-1 could significantly inhibit the proliferation and MIF tautomerase activity of human ovarian cancer cells (SKOV3 and A2780) (P <0.05), and both showed a positive correlation (SKOV3: r = 0.841, r = 0.862, P <0.01). After being treated with 50μmol / L ISO-1 for 24 h, the ability of penetrating through the polycarbonate membrane was significantly decreased (P <0.05), while the ovarian cancer cells CD74, VEGFR-2 mRNA levels were significantly lower (P <0.05). Conclusion ISO-1 can down-regulate the expression of VEGF and VEGFR-2 by inhibiting the activity of CD74, thereby inhibiting the proliferation and invasion of ovarian cancer cells.