RRC ID 51602
著者 Tadokoro T, Morishita A, Fujihara S, Iwama H, Niki T, Fujita K, Akashi E, Mimura S, Oura K, Sakamoto T, Nomura T, Tani J, Miyoshi H, Yoneyama H, Himoto T, Hirashima M, Masaki T.
タイトル Galectin-9: An anticancer molecule for gallbladder carcinoma.
ジャーナル Int J Oncol
Abstract Gallbladder cancer (GBC) is the most common and aggressive type of biliary tract cancer. There are various histological types of GBC, and the vast majority of GBC cases are adenocarcinomas. Squamous and adenosquamous carcinomas are rare GBC subtypes that are traditionally considered to be more aggressive and to be associated with a poorer prognosis than adenocarcinoma. Galectin-9 (Gal-9), a tandem-repeat-type galectin, has been reported to induce apoptosis-mediated elimination of various cancers, including hepatocellular carcinoma, cholangiocarcinoma, and hematologic malignancies. Therefore, we investigated the antitumor effects of Gal-9 on GBC in vitro and in vivo. In our in vitro experiments, Gal-9 suppressed cell proliferation in various GBC cell lines but not in the OCUG-1 cell line, which represents a poorly differentiated type of adenosquamous carcinoma. Gal-9 induced the apoptosis of Gal-9-sensitive GBC cells by increasing the levels of caspase-cleaved keratin 18 and phosphorylated p53. However, Gal-9 did not affect the expression of various cell cycle-related proteins. In addition, Gal-9 suppressed tumor growth by implanted human GBC cells in a xenograft model. Furthermore, Gal-9 induced the phosphorylation of the Ephrin type-B receptor, and the microRNA (miRNA) expression profile was markedly altered by Gal-9. Based on these results, various miRNAs might contribute to the suppression of tumor growth. Our data reveal that Gal-9 suppresses the growth of GBC, possibly by inducing apoptosis and altering miRNA expression. Thus, Gal-9 might serve as a therapeutic agent for the treatment of GBC.
巻・号 48(3)
ページ 1165-74
公開日 2016-3-1
DOI 10.3892/ijo.2016.3347
PMID 26797414
MeSH Animals Apoptosis Carcinoma / drug therapy* Carcinoma / metabolism* Cell Differentiation Cell Proliferation Enzyme-Linked Immunosorbent Assay Female Galectins / metabolism* Gallbladder Neoplasms / drug therapy* Gallbladder Neoplasms / metabolism* Gene Expression Regulation, Neoplastic* Humans Keratin-18 / metabolism Mice Mice, Inbred BALB C MicroRNAs / metabolism Mutation Phosphorylation Xenograft Model Antitumor Assays
IF 3.899
引用数 17
リソース情報
ヒト・動物細胞 G-415(RCB2640) TGBC24TKB(RCB1196)