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Enhanced interleukin-2 diphtheria toxin conjugate-induced growth suppression in retinoic acid-treated hypoxic hepatocellular carcinoma cells
Cited 3 time in
Web of Science
Cited 5 time in Scopus
- Authors
- Issue Date
- 2009-02-18
- Publisher
- ELSEVIER IRELAND LTD
- Citation
- CANCER LETTERS; Vol.274 2; 259-265
- Keywords
- Hypoxia ; Retinoic acid ; Interleukin-2 ; Interleukin-2 diphteria toxin conjugate ; Hepatocellular carcinoma
- Abstract
- 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.
- ISSN
- 0304-3835
- Language
- English
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