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

作者：Lee Jeong Hoon; Yoon Jung Hwan^*; Yu Su Jong; Chung Goh Eun; Jung Eun Uk; Kim Hwi Young; Kim Bo Hyun; Choi Dae Hee; Myung Sun Jung; Kim Yoon Jun; Kim Chung Yong; Lee Hyo Suk

来源：Cancer Letters, 2010, 295(2): 229-235.

DOI：10.1016/j.canlet.2010.03.005

• Cellular retinoic acid binding protein-II
• Retinoic acid
• Hepatocellular carcinoma
• Apoptosis
• Hypoxia

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.

• 出版日期2010-9-28