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- Title
Anti‐tumor effects of a nonsteroidal anti‐inflammatory drug zaltoprofen on chondrosarcoma via activating peroxisome proliferator‐activated receptor gamma and suppressing matrix metalloproteinase‐2 expression.
- Authors
Higuchi, Takashi; Takeuchi, Akihiko; Munesue, Seiichi; Yamamoto, Norio; Hayashi, Katsuhiro; Kimura, Hiroaki; Miwa, Shinji; Inatani, Hiroyuki; Shimozaki, Shingo; Kato, Takashi; Aoki, Yu; Abe, Kensaku; Taniguchi, Yuta; Aiba, Hisaki; Murakami, Hideki; Harashima, Ai; Yamamoto, Yasuhiko; Tsuchiya, Hiroyuki
- Abstract
Abstract: Surgical resection is the only treatment for chondrosarcomas, because of their resistance to chemotherapy and radiotherapy; therefore, additional strategies are crucial to treat chondrosarcomas. Peroxisome proliferator‐activated receptor gamma (PPAR<italic>γ</italic>) is a ligand‐activated transcription factor, which has been reported as a possible therapeutic target in certain malignancies including chondrosarcomas. In this study, we demonstrated that a nonsteroidal anti‐inflammatory drug, zaltoprofen, could induce PPAR<italic>γ</italic> activation and elicit anti‐tumor effects in chondrosarcoma cells. Zaltoprofen was found to induce expressions of PPAR<italic>γ </italic>mRNA and protein in human chondrosarcoma SW1353 and OUMS27 cells, and induce PPAR<italic>γ</italic>‐responsible promoter reporter activities. Inhibitory effects of zaltoprofen were observed on cell viability, proliferation, migration, and invasion, and the activity of matrix metalloproteinase‐2 (MMP2); these effects were dependent on PPAR<italic>γ</italic> activation and evidenced by silencing PPAR<italic>γ</italic>. Moreover, we showed a case of a patient with cervical chondrosarcoma (grade 2), who was treated with zaltoprofen and has been free from disease progression for more than 2 years. Histopathological findings revealed enhanced expression of PPAR<italic>γ</italic> and reduced expression of MMP2 after administration of zaltoprofen. These findings demonstrate that zaltoprofen could be a promising drug against the malignant phenotypes in chondrosarcomas via activation of PPAR<italic>γ</italic> and inhibition of MMP2 activity.
- Subjects
CHONDROSARCOMA; CELL proliferation; CELL survival; PEROXISOME proliferator-activated receptors; MATRIX metalloproteinases; SURGICAL excision; THERAPEUTICS
- Publication
Cancer Medicine, 2018, Vol 7, Issue 5, p1944
- ISSN
2045-7634
- Publication type
Article
- DOI
10.1002/cam4.1438