Premium
Sensitization by interleukin‐lα of carboplatinum anti‐tumor activity against human ovarian (NIH:OVCAR‐3) carcinoma cells in vitro and in vivo
Author(s) -
Wang Zheng,
Lee Kang Bo,
Reed Eddie,
Sinha Biranda K.
Publication year - 1996
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/(sici)1097-0215(19961127)68:5<583::aid-ijc5>3.0.co;2-v
Subject(s) - carboplatin , cytotoxicity , ovarian carcinoma , in vivo , cisplatin , cancer research , ovarian cancer , cytotoxic t cell , in vitro , nitric oxide , chemistry , pharmacology , immunology , biology , medicine , endocrinology , cancer , chemotherapy , biochemistry , microbiology and biotechnology
Cytokines are directly cytotoxic to tumor cells in vitro and in vivo , and interleukin‐1α (IL‐1α) 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 IL‐1α 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‐1α 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‐1α or followed by carboplatin caused a significant delay in tumor growth, resulting in a significant enhancement (4‐fold) of the anti‐tumor effect of carboplatin. In vitro potentiation of carboplatin cytotoxicity by IL‐1α did not involve formation of nitric oxide as IL‐1α or combinations of IL‐1α with carboplatin failed to modulate basal nitric oxide production in OVCAR‐3 cells. Potentiation of the anti‐tumor activity of carboplatin by IL‐1α was due to a significant (3‐ to 4‐fold) increase in the accumulation of total Pt in IL‐1α‐treated tumor xenograft, resulting in a 2‐fold increase in DNA‐Pt adduct formation in these tumors. In contrast, IL‐1α had no significant effect on DNA‐Pt adduct formation in the kidney. The potent synergy of IL‐ I1α and carboplatin in vitro and in vivo against ovarian carcinoma cells suggests that combinations of carboplatinum and interleukin‐1α may be effective against this disease in the clinic. (This article is a US Government work and. as such. is in the public domain in the United States of America.) © 1996 Wiley‐Liss, Inc.