In vitro modulation of MMP-2 and MMP-9 in human cervical and ovarian cancer cell lines by cytokines, inducers and inhibitors.
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 24 h 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-alpha and interleukin-1beta, 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.
Roomi
M W
MW
Dr Rath Research Institute, Santa Clara, CA 95050, USA.
Monterrey
J C
JC
Kalinovsky
T
T
Rath
M
M
Niedzwiecki
A
A
D002392:Catechin / Q000031:analogs & derivatives / Q000494:pharmacology; D045744:Cell Line, Tumor; D016207:Cytokines / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004318:Doxycycline / Q000494:pharmacology; D004790:Enzyme Induction; D005260:Female; D006801:Humans; D053583:Interleukin-1beta / Q000494:pharmacology; D008070:Lipopolysaccharides / Q000494:pharmacology; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism*; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism*; D061965:Matrix Metalloproteinase Inhibitors; D010051:Ovarian Neoplasms / Q000201:enzymology*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology; D002583:Uterine Cervical Neoplasms / Q000201:enzymology*
D016207:Cytokines; D053583:Interleukin-1beta; D008070:Lipopolysaccharides; D061965:Matrix Metalloproteinase Inhibitors; D014409:Tumor Necrosis Factor-alpha; D002392:Catechin; C045651:epigallocatechin gallate; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9; D004318:Doxycycline; D013755:Tetradecanoylphorbol Acetate