Sensitization by interleukin-lα of carboplatinum anti-tumor activity against human ovarian (NIH:OVCAR-3) carcinoma cells in vitro and in vivo
✍ Scribed by Zheng Wang; Kang Bo Lee; Eddie Reed; Biranda K. Sinha
- Publisher
- John Wiley and Sons
- Year
- 1996
- Tongue
- French
- Weight
- 513 KB
- Volume
- 68
- Category
- Article
- ISSN
- 0020-7136
No coin nor oath required. For personal study only.
✦ Synopsis
Cytokines are directly cytotoxic to tumor cells in vitro and in vivo, and interleukinla (ILla) potentiates the cytotoxicity of a number of clinically active drugs in several human tumor cells, including carcinomas of the breast and ovary. In this study, we found that ILla potentiated the cytotoxicity of carboplatin in human ovarian NIH:OVCAR-3 cancer cells during simultaneous drug exposure in vitro. Human ovarian carcinoma NIH:OVCAR-3 cells are resistant to clinically relevant concentrations of chemotherapeutic agents, including cisplatin. Both carboplatin and IL-la as single agents inhibited the growth of NIH:OVCAR-3 cells grown as xenograft in nude mice; however, carboplatin was more effective in delaying tumor growth, and this inhibition was dose-dependent. Treatment with IL-I a followed by carboplatin caused a significant delay in tumor growth, resulting in a signifiiant enhancement (4-fold) of the anti-tumor effect of carboplatin. In vitro potentiation of carboplatin cytotoxicity by IL-la did not involve formation of nitric oxide as IL-I or combinations of IL-l with carboplatin failed to modulate basal nitric oxide production in OVCAR-3 cells. Potentiation of the anti-tumor activity of carboplatin by IL-la was due to a significant (3to 4-fold) increase in the accumulation of total Pt in IL-I-treated tumor xenograft, resulting in a 2-fold increase in DNA-Pt adduct formation in these tumors. In contrast, IL-la had no significant effect on DNA-Pt adduct formation in the kidney. The potent synergy of IL-I a and carboplatin in vitro and in vhro against ovarian carcinoma cells suggests that combinations of carboplatinum and interleukin-la may be effective against this disease in the clinic. o 1996 Wiley-Liss, Inc. * Cytokines are important biochemical modulators that caneither sensitize tumor cells to the effects of other anti-cancer drugs or exert direct cytotoxic effects on tumor cells. IL-1, produced by activated monocytes and macrophages, directly inhibits the proliferation of certain tumor cells and exerts anti-tumor activity indirectly by enhancing cellular immune