Effect Of Matrix Metalloproteinase Inhibitor Ilomastat Combined With Chemotherapeutic Drugs On Human Laryngeal Cancer Hep-2Cell

Objective：To analyze the effect of the matrix metalloproteinase inhibitorlomastat combined with chemotherapeutic drugs on proliferation and apotosis ofhuman laryngeal cancer Hep-2cell,and preliminarily explore the mechanism ofIlomastat on invasion of laryngeal carcinoma, providing a reference for combinedchemotherapy of laryngeal cancer.Methods：Ilomastat,Capecitabine alone and in combination were given to Hep-2cell, untreated group was control group.The proliferation activity of the Hep-2cellswas analyzed by MTT assay,and using the Jin’s Q assessed the interaction betweenIlomastat and Capecitabine; flow cytometry detected the apoptosis rate of Hep-2cell;the expression level of MMP-9mRNA in Hep-2cell was detected by RT-PCR.Result：①MTT assay showed different concentrations of Ilomastat andCapecitabine were all able to inhibit the proliferation of Hep-2cell,and the inhibitionspresented dose-dependent(P<0.05); the combination of Ilomastat and Capecitabineincreased the inhibitory effect(P<0.05), the interaction between Ilomastat andCapecitabine was synergistic effect when the combined concentration was8μg/mLIlomastat combined with100μg/ml Capecitabine, while the interaction betweenIlomastat and Capecitabine was additive action when the combined concentration was40μg/mL Ilomastat combined with400μg/ml Capecitabine;②flow cytometryindicated that the apoptosis rate of Hep-2cell in the single Ilomastat group and singleCapecitabine group were both higher than the control group(P<0.05), and in the drugcombination group the apoptosis rate was higher than the other groups(P<0.05);③RT-PCR analysis showed that compared with control group, the expression level ofMMP-9mRNA in the single Ilomastat group and drug combination group were bothdecreased(P<0.05), and the expression of MMP-9mRNA in the drug combinationgroup was lower than the single Ilomastat group(P<0.05),but there was no statisticdifference between the single Capecitabine group and the control group in theexpression level of MMP-9mRNA.Conclusion：Ilomastat combined with Capecitabine can obviously enhance the inhibition and apoptosis-induced ability of single drug on laryngeal cancer Hep-2cell;it is speculated that the mechanism of Ilomastat is down-regulation of the expressionlevel of the MMP-9mRNA.