期刊
CANCER LETTERS
卷 274, 期 2, 页码 259-265出版社
ELSEVIER IRELAND LTD
DOI: 10.1016/j.canlet.2008.09.025
关键词
Hypoxia; Interleukin-2; Interleukin-2 diphteria toxin conjugate; Hepatocellular carcinoma; Retinoic acid
类别
资金
- Seoul National University Hospital Research Fund [03-2006-019]
- Korea Health 21 RD [0412-CR01-0704-0001]
Hypoxia induces survival signals in hepatocellular carcinoma (HCC). Hypoxia and retinoic acid (RA) may also induce interleukin-2 (IL-2) receptor expression, and thus we evaluated if RA and IL-2 receptor-targeted therapy are indicated in hypoxic HCCs. RA induced IL-2 receptor expression (R alpha, R beta, R gamma) in HCC cells, whereas hypoxia specifically induced IL-2 R gamma expression. IL-2 stimulated hypoxic HCC cell growth via p42/44 MAPK activation. Combination of denileukin diftitox and RA significantly suppressed hypoxic HCC cell growth compared to single agent-treated or normoxic cells. Therefore, denileukin diftitox and RA may be therapeutically implicated in infiltrative HCCs which are exposed to hypoxic environments. (C) 2008 Elsevier Ireland Ltd. All rights reserved.
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