PT  - JOURNAL ARTICLE
AU  - Xin Xin Xiong
AU  - Xin Yao Qiu
AU  - Dian Xing Hu
AU  - Xiao Qian Chen
TI  - Advances in Hypoxia-mediated Mechanisms in Hepatocellular Carcinoma
AID  - 10.1124/mol.116.107706
DP  - 2017 Jan 01
TA  - Molecular Pharmacology
PG  - mol.116.107706
4099  - http://molpharm.aspetjournals.org/content/early/2017/02/27/mol.116.107706.short
4100  - http://molpharm.aspetjournals.org/content/early/2017/02/27/mol.116.107706.full
AB  - Hepatocellular carcinoma (HCC) is the fifth most common and the third most deadly malignant tumor worldwide. Hypoxia and related oxidative stress are heavily involved in the process of HCC development and therapies. However, direct and accurate measuring oxygen concentration and evaluating hypoxic effects in HCC prove difficult. Moreover, the hypoxia-mediated mechanisms in HCC remain elusive. Here, we summarize recent major evidence of hypoxia in HCC lesions by measuring pO2, the clinical importance of hypoxic markers in HCC, and recent advances in hypoxia-related mechanisms and therapies in HCC. For the mechanisms, we focus mainly on the roles of oxygen-sensing proteins (i.e., hypoxia inducible factor and neuroglogin) and hypoxia-induced signaling proteins (e.g., matrix metalloproteinases, high mobility group box 1, Beclin 1, glucose metabolism enzymes, and vascular endothelial growth factor). With respect to therapies, we discuss mainly YQ23, Sorafenib, 2-Methoxyestradiol and Celastrol. This review focuses primarily on the results of clinical and animal studies.