Journal
CANCER MEDICINE
Volume 7, Issue 5, Pages 1944-1954Publisher
WILEY
DOI: 10.1002/cam4.1438
Keywords
Chondrosarcoma; MMP2; nonsteroidal anti-inflammatory drugs; PPAR gamma; zaltoprofen
Categories
Funding
- Japan Society for the Promotion of Science [JP15K10435, JP17K16682]
- Grants-in-Aid for Scientific Research [15K10435] Funding Source: KAKEN
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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 gamma) 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 antiinflammatory drug, zaltoprofen, could induce PPAR gamma activation and elicit anti-tumor effects in chondrosarcoma cells. Zaltoprofen was found to induce expressions of PPAR gamma mRNA and protein in human chondrosarcoma SW1353 and OUMS27 cells, and induce PPAR gamma-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 gamma activation and evidenced by silencing PPAR gamma. 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 gamma 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 gamma and inhibition of MMP2 activity.
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