Pentoxifylline enhances sensitivity of a human ovarian cancer cell line (OVC-8) to TNF-alpha.
The OVC-8 human ovarian cancer cell line constitutively expresses tumor necrosis factor alpha (TNF-alpha) mRNA and protein and is resistant to TNF-alpha. When OVC-8 cells are treated with pentoxifylline (PTX), the level of mRNA for TNF-alpha is markedly reduced. Combination treatment of OVC-8 cells with PTX and TNF-alpha overcomes the resistance. PTX-treatment has no effect on the expression of TNF-alpha mRNA in C30 cells, which do not constitutively express TNF-alpha mRNA. The combination of PTX and TNF-alpha do not overcome the resistance of C30 cells to TNF-alpha. PTX or anti-TNF-alpha monoclonal antibody has no effect on the growth of OVC-8 cells, suggesting that the growth of OVC-8 cells does not depend upon an autocrine action of TNF-alpha. The synergistic cytotoxic effect obtained with ovarian cancer cells suggests that the combination of PTX and TNF-alpha could be applied clinically in the therapy of TNF-alpha-producing ovarian cancer.
Mizutani
Y
Y
Department of Microbiology and Immunology, UCLA School of Medicine, University of California at Los Angeles 90024.
Bonavida
B
B
D000911:Antibodies, Monoclonal / Q000276:immunology; D004317:Doxorubicin / Q000494:pharmacology; D005260:Female; D006801:Humans; D010051:Ovarian Neoplasms / Q000473:pathology / Q000628:therapy*; D010431:Pentoxifylline / Q000494:pharmacology*; D012333:RNA, Messenger / Q000032:analysis; D014407:Tumor Cells, Cultured / Q000187:drug effects; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000494:pharmacology*
D000911:Antibodies, Monoclonal; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D004317:Doxorubicin; D010431:Pentoxifylline