Open AccessAnti‐tumor effects of a nonsteroidal anti‐inflammatory drug zaltoprofen on chondrosarcoma via activating peroxisome proliferator‐activated receptor gamma and suppressing matrix metalloproteinase‐2 expression
Author(s) -
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
Publication year - 2018
Publication title -
cancer medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.403
H-Index - 53
ISSN - 2045-7634
DOI - 10.1002/cam4.1438
Subject(s) - peroxisome proliferator activated receptor , cancer research , chondrosarcoma , gene silencing , matrix metalloproteinase , receptor , chemistry , biology , medicine , pathology , biochemistry , gene
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 γ ) 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 γ activation and elicit anti‐tumor effects in chondrosarcoma cells. Zaltoprofen was found to induce expressions of PPAR γ mRNA and protein in human chondrosarcoma SW 1353 and OUMS 27 cells, and induce PPAR γ ‐responsible promoter reporter activities. Inhibitory effects of zaltoprofen were observed on cell viability, proliferation, migration, and invasion, and the activity of matrix metalloproteinase‐2 ( MMP 2); these effects were dependent on PPAR γ activation and evidenced by silencing PPAR γ . 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 γ and reduced expression of MMP 2 after administration of zaltoprofen. These findings demonstrate that zaltoprofen could be a promising drug against the malignant phenotypes in chondrosarcomas via activation of PPAR γ and inhibition of MMP 2 activity.