Abstract:

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 (P<0.05), and the MIF tautomerase activities positively correlated with the proliferation of the ovarian cancer cells affected by ISO-1(SKOV3: r=0.841, P<0.01; A2780: r=0.862, P<0.01).The number of invaded SKOV3 and A2780 cells was significantly less in the group treated by 50μmol/L ISO-1 for 24h than that in the control group(P<0.05). The expression of CD74、VEGFR-2 mRNA was obviously reduced after ISO-1 treatment(P<0.05). 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.

Key words: ISO-1; Ovarian cancer; Macrophage migration inhibition factor; Vascular endothelial growth factor receptor-2; CD74