Retinoic acid and its binding protein modulate apoptotic signals in hypoxic hepatocellular carcinoma cells

被引：11

作者：

Lee, Jeong-Hoon ^{[1
,2
]}

Yoon, Jung-Hwan ^{[1
,2
]}

Yu, Su Jong ^{[1
,2
]}

Chung, Goh Eun ^{[1
,2
]}

Jung, Eun Uk ^{[3
]}

Kim, Hwi Young ^{[1
,2
]}

Kim, Bo Hyun ^{[4
,5
]}

Choi, Dae Hee ^{[6
]}

Myung, Sun Jung ^{[1
,2
]}

Kim, Yoon Jun ^{[1
,2
]}

Kim, Chung Yong ^{[1
,2
]}

Lee, Hyo-Suk ^{[1
,2
]}

机构：

[1] Seoul Natl Univ, Coll Med, Dept Internal Med, Seoul 151, South Korea

[2] Seoul Natl Univ, Coll Med, Liver Res Inst, Seoul 151, South Korea

[3] Inje Univ, Dept Internal Med, Busan Paik Hosp, Coll Med, Pusan, South Korea

[4] Bundang Jesaeng Gen Hosp, Dept Internal Med, Songnam, South Korea

[5] Bundang Jesaeng Gen Hosp, Hepatol Ctr, Songnam, South Korea

[6] Kangwon Natl Univ, Coll Med, Dept Internal Med, Chunchon, South Korea

来源：

CANCER LETTERS | 2010年 / 295卷 / 02期

关键词：

Cellular retinoic acid binding protein-II; Retinoic acid; Hepatocellular carcinoma; Apoptosis; Hypoxia; 2ND PRIMARY TUMORS; ENDOPLASMIC-RETICULUM STRESS; GENE-EXPRESSION; HEPATOMA-CELLS; BREAST-CANCER; GROWTH; PROLIFERATION; PREVENTION; INDUCTION; KINASE;

D O I：

10.1016/j.canlet.2010.03.005

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

Hypoxia induces survival signals in hepatocellular carcinoma (HCC). We attempted to find a hypoxia-induced signal that could be used for modulating HCC cell death. Cellular retinoic acid binding protein-II (CRABP-II) expression was significantly increased in hypoxic HCC cells. Treatment with retinoic acid (RA), a ligand for CRABP-II, induced HCC cell apoptosis more effectively in hypoxia than in normoxia, whereas hypoxia-induced CRABP-II expression attenuated RA-induced apoptosis. Inhibition of CRABP-II enhanced RA-induced apoptosis and sensitized RA-resistant HCC cells to RA cytotoxicity by attenuating p42/44 MAPK and Akt activation. Therefore, RA/CRABP-II signal modulation is therapeutically implicated in infiltrative HCCs exposed to hypoxia. (C) 2010 Elsevier Ireland Ltd. All rights reserved.

引用

页码：229 / 235

页数：7

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