title: Enhanced interleukin-2 diphtheria toxin conjugate-induced growth suppression in retinoic acid-treated hypoxic hepatocellular carcinoma cells.
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.
authors.affiliation: Department of Internal Medicine and the Liver Research Institute, Seoul National University College of Medicine, 28 Yungun-dong, Chongno-gu, Seoul 110-744, Republic of Korea.
authors.forename: Bo Hyun
authors.initials: BH
authors.lastname: Kim
authors.forename: Jung-Hwan
authors.initials: JH
authors.lastname: Yoon
authors.forename: Sun Jung
authors.initials: SJ
authors.lastname: Myung
authors.forename: Jeong-Hoon
authors.initials: JH
authors.lastname: Lee
authors.forename: Sung-Hee
authors.initials: SH
authors.lastname: Lee
authors.forename: Soo-Mi
authors.initials: SM
authors.lastname: Lee
authors.forename: Hyo-Suk
authors.initials: HS
authors.lastname: Lee
mesh_terms: D015153:Blotting, Western; D006528:Carcinoma, Hepatocellular / Q000201:enzymology / Q000473:pathology*; D002455:Cell Division / Q000187:drug effects*; D015687:Cell Hypoxia; D045744:Cell Line, Tumor; D004167:Diphtheria Toxin / Q000737:chemistry / Q000494:pharmacology*; D004789:Enzyme Activation; D006801:Humans; D007376:Interleukin-2 / Q000737:chemistry / Q000494:pharmacology*; D008113:Liver Neoplasms / Q000201:enzymology / Q000473:pathology*; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D014212:Tretinoin / Q000494:pharmacology*
chemical_list: D004167:Diphtheria Toxin; D007376:Interleukin-2; D014212:Tretinoin; D020928:Mitogen-Activated Protein Kinases