Modulation of MMP-2 and MMP-9 by cytokines, mitogens and inhibitors in lung cancer and malignant mesothelioma cell lines

At near confluence, the cells were washed with PBS and incubated in serum- free medium with various concentrations of several cytokines, mitogens and inhibitors. After 24h the media were removed and analyzed for MMP-2 and MMP-9 by gelatinase zymography and quantitated by densitometry. LC expressed MMP-2, whereas MM expressed MMP-2 and MMP-9. TNF-, IL-1, LPS, and PMA stimulated MMP-2 in LC and inhibited MMP-2 in MM. Doxycycline, EGCG and NM inhibited MMP–2 and MMP–9 expression, in both cell lines. Actinomycin-D, cyclohexamide, retinoic acid, and dexamethasone inhibited MMP-2 in both cancer cell lines and inhibited MMP-9 in MM. Our results show that cytokines and inhibitors have an up- or down-regulatory effect on MMP-2 and MMP-9 expression in LC and MM, suggesting the clinical value of targeting these proteases for the management of LC and MM and their pathogenesis.

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