Synergistic antitumor effects of celecoxib with 5-fluorouracil depend on IFN-γ
| Autor: | Shingo Tsuji, Shinichiro Shinzaki, Masakazu Yasumaru, Norio Hayashi, Tsutomu Nishida, Satoshi Egawa, Hideki Iijima, Masahiko Tsujii, Takanobu Irie, Hiroaki Murata, Toshiyuki Yoshio, Tetsuo Takehara, Yoshimi Kakiuchi, Sunao Kawano, Shuji Ishii |
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| Rok vydání: | 2007 |
| Předmět: |
Male
Vascular Endothelial Growth Factor A musculoskeletal diseases Cancer Research medicine.medical_specialty Angiogenesis Colorectal cancer medicine.drug_class medicine.medical_treatment Thymidylate synthase Antimetabolite Interferon-gamma Mice Internal medicine Antineoplastic Combined Chemotherapy Protocols Animals Medicine heterocyclic compounds skin and connective tissue diseases Mice Knockout Mice Inbred BALB C Sulfonamides Chemotherapy Cyclooxygenase 2 Inhibitors Neovascularization Pathologic biology business.industry organic chemicals medicine.disease Endocrinology Oncology Celecoxib Enzyme inhibitor Fluorouracil Colonic Neoplasms biology.protein Cancer research Pyrazoles lipids (amino acids peptides and proteins) Drug Screening Assays Antitumor business medicine.drug |
| Zdroj: | International Journal of Cancer. 121:878-883 |
| ISSN: | 1097-0215 0020-7136 |
| DOI: | 10.1002/ijc.22720 |
| Popis: | Cyclooxygenase-2 (COX-2) inhibitors are effective chemopreventive agents against colorectal cancers. For treatment of advanced cancers, combination of COX-2 inhibitors and chemotherapy has been attempted, but the results are still controversial. In the present study, the effects of the COX-2 inhibitor celecoxib on the anticancer potential of chemotherapy, and its mechanisms of action were investigated in point of the angiogenesis, using an advanced cancer model in mice. BALB/c mice were inoculated with colon 26 cells. After the allograft grew up to 5 mm in diameter, the animals received celecoxib, 5FU, or a combination of 5FU and celecoxib (5FU/celecoxib). After 21-days of the treatment, 5FU/celecoxib significantly inhibited the tumor growth and the tumor vessel density compared with the other groups. Celecoxib, 5FU or 5FU/celecoxib significantly suppressed the VEGF content in tumor tissues. 5FU/celecoxib also enhanced IFN-γ levels in tumor tissue, which could be involved in the potent antitumor effects of 5FU/celecoxib. This hypothesis was proven, because in IFN-γ knockout (IFN-γ−/−) mice, the inhibitory effects of 5FU/celecoxib on angiogenesis and tumor growth were significantly impaired compared with that in wild type mice. These results suggest that celecoxib enhances the antitumor effect of 5FU against an advanced colon cancer model by suppressing angiogenesis. In addition to VEGF, IFN-γ has pivotal roles in tumor suppression induced by celecoxib. © 2007 Wiley-Liss, Inc. |
| Databáze: | OpenAIRE |
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