Galectin-9 suppresses cholangiocarcinoma cell proliferation by inducing apoptosis but not cell cycle arrest

被引：43

作者：

Kobayashi, Kiyoyuki ^{[1
]}

Morishita, Asahiro ^{[1
]}

Iwama, Hisakazu ^{[2
]}

Fujita, Koji ^{[1
]}

Okura, Ryoichi ^{[1
]}

Fujihara, Shintaro ^{[1
]}

Yamashita, Takuma ^{[1
]}

Fujimori, Takayuki ^{[1
]}

Kato, Kiyohito ^{[1
]}

Kamada, Hideki ^{[1
]}

Niki, Toshiro ^{[3
]}

Hirashima, Mitsuomi ^{[3
]}

Okano, Kehchi ^{[4
]}

Suzuki, Yasuyuki ^{[4
]}

Masaki, Tsutomu ^{[1
]}

机构：

[1] Kagawa Univ, Fac Med, Dept Gastroenterol & Neurol, Miki, Kagawa 7610793, Japan

[2] Kagawa Univ, Fac Med, Life Sci Res Ctr, Miki, Kagawa 7610793, Japan

[3] Kagawa Univ, Fac Med, Dept Immunol, Miki, Kagawa 7610793, Japan

[4] Kagawa Univ, Fac Med, Dept Surg Gastroenterol, Miki, Kagawa 7610793, Japan

来源：

ONCOLOGY REPORTS | 2015年 / 34卷 / 04期

关键词：

cholangiocarcinoma; galectin-9; apoptosis; cell cycle; microRNAs; cytochrome c; epidermal growth factor receptor; angiogenesis; DENDRITIC CELLS; UNITED-STATES; T-CELLS; CANCER; DEATH; MICRORNA-198; RESISTANCE; ECALECTIN; PROTEINS; PATHWAY;

D O I：

10.3892/or.2015.4197

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

Cholangiocarcinoma is the most common biliary malignancy and the second most common hepatic malignancy after hepatocellular carcinoma (HCC). Galectin-9 (Gal-9) is a tandem-repeat-type galectin that has recently been shown to exert antiproliferative effects on cancer cells. Therefore, the present study evaluated the effects of Gal-9 on the proliferation of human cholangiocarcinoma cells in vitro as well as the microRNAs (miRNAs) associated with the antitumor effects of Gal-9. Gal-9 suppressed the proliferation of cholangiocarcinoma cell lines in vitro and the growth of human cholangiocarcinoma cell xenografts in nude mice. Our data further revealed that Gal-9 increased caspase-cleaved keratin 18 (CCK18) levels, and the expression of cytochrome c increased in Gal-9-treated cholangiocarcinoma cell lines. These data suggested that Gal-9 induced cholangiocarcinoma cell apoptosis via the intrinsic apoptosis pathway mediated by caspase-dependent or -independent pathways. In addition, Gal-9 reduced the phosphorylation of the epidermal growth factor receptor (EGFR), insulin-like growth factor and insulin-like growth factor-1 receptor (IGF-1R), hepatocyte growth factor receptor and fibroblast growth factor receptor 3 (FGFR3). These findings suggest that Gal-9 can be a candidate of therapeutic target in the treatment of cholangiocarcinoma.

引用

页码：1761 / 1770

页数：10

共 34 条

[1] Qualification of M30 and M65 ELISAs as surrogate biomarkers of cell death: long term antigen stability in cancer patient plasma [J].