In Vitro Modulation of MMP-2 and MMP-9 in Human Cervical and Ovarian Cancer Cell Lines by Cytokines, Inducers, and Inhibitors

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M.W. Roomi, J.C. Monterrey, T. Kalinovsky, M. Rath, A. Niedzwiecki
Oncology Reports 2010, 23: 605-614

Matrix  metalloproteinases (MMPs) secreted by cervical and ovarian cancer, especially  MMP-2 and MMP-9, play crucial roles in tumor invasion and metastasis. We examined the effect of cytokines, mitogens, inducers and inhibitors on MMP-2 and MMP-9 expression in cervical and ovarian cancer cell lines. Human cervical (Hela and DoTc2-4510) and ovarian (SK-OV-3) cell lines were cultured in appropriate media. 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.

Hela and SK-OV-3 cell lines expressed MMP-2 whereas DoTc2-4510 cells expressed MMP-9. Treatment of cervical cancer cell lines (Hela and DoTc2-4510) with PMA had no effect on MMP-2 expression, and a moderate stimulatory effect in ovarian cancer cell line SK-OV-3. MMP-9 was stimulated by phorbol 12-myristate 13-acetate in Hela cells and enhanced in DoTc2-4510. Tumor necrosis factor-α, and interleukin-1β, had slight inhibitory effect on Hela cell expression of MMP-2 while lipopolysaccharide stimulated MMP-2 in Hela cells. Doxycycline, epigallocatechin gallate, a nutrient mixture, actinomycin-D, cyclohexamide, retinoic acid, and dexamethasone inhibited MMP-2 in Hela and SK-OV-3 cell lines and inhibited MMP-9 in DoTc2-4510. Our results show that cytokines, mitogens, inducers and inhibitors have an up or down regulatory effect on MMP-2 and MMP-9 expression in ovarian and cervical cancer cell lines, suggesting these agents may be effective strategies to treat these cancers.

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