SGLT2阻害剤CanagliflozinはAMPK-mTORシグナルを介してglioblastomaの増殖を制御する

• Published in: 日本薬理学会年会要旨集 p. 1-B-P-080
• Main Authors: 江田, 岳誉, 棗田, 学, 大石, 誠, 藤井, 幸彦, 武井, 延之
• Format: Journal Article
• Language: Japanese
• Published: 公益社団法人 日本薬理学会 2022
• Subjects: antidiabetic; drug efficacy; energy metabolism; glioma cell
• ISSN: 2435-4953
• DOI: 10.1254/jpssuppl.96.0_1-B-P-080

Glucose is a major metabolic source required for cancer cell survival and growth. The up-take of glucose by its transporters is enhanced in cancer cells. Cellular glucose levels are sensed by 5′-AMP-activated protein kinase (AMPK). Upon glucose insufficiency, AMPK is activated and suppresses anabolic processes such as mammalian target of rapamycin (mTOR) system. mTOR is a key molecule for cellular growth and dysregulated activation is observed in cancer cells. Therefore, we focused on the sodium-glucose transporter 2 (SGLT2) in glioblastoma survival and growth, because its expression was observed in these cells. We examined the effects of pharmacological inhibition of SGLT2 by canagliflozin. Canagliflozin reduced the growth of glioblastoma cell lines of human origin in a dose-dependent manner. Canagliflozin enhanced the phosphorylation of AMPK and suppressed S6 protein and p70S6 kinase phosphorylation. Canagliflozin inhibited the protein synthesis evaluated by the SUnSET assay. Canagliflozin inhibited the growth of glioblastoma also in xenograft model. Canagliflozin activates AMPK and inhibits mTOR pathway thus inhibits the glioblastoma growth both in vitro and in vivo.