TNF-alpha mediates inducible nitric oxide synthase expression in human neuroblastoma cell line by cisplatin.
The human neuroblastoma cell line NB-39-nu expressed inducible nitric oxide synthase (iNOS) mRNA following treatment with a combination of interferon-gamma (IFN-gamma) and cis-diamminedichloroplatinum(II) (cisplatin). The level of iNOS mRNA peaked at 48 hr after treatment, and dexamethasone inhibited the induction of iNOS mRNA expression. Cisplatin induced tumor necrosis factor-alpha (TNF-alpha) mRNA expression, and an anti-TNF-alpha neutralizing antibody inhibited the induction of iNOS expression by a combination of cisplatin and IFN-gamma in NB-39-nu cells. Thus, iNOS expression in NB-39-nu cells by a combination of cisplatin and IFN-gamma involves in the TNF-alpha-mediated signal transduction mechanism.
Ogura
T
T
Investigative Treatment Division, National Cancer Center Research Institute, Chiba, Japan. togura@east.ncc.go.jp
Tatemichi
M
M
Esumi
H
H
D000970:Antineoplastic Agents / Q000633:toxicity*; D001483:Base Sequence; D002945:Cisplatin / Q000633:toxicity*; D017931:DNA Primers / Q000235:genetics; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D009447:Neuroblastoma / Q000201:enzymology / Q000235:genetics; D009474:Neurons / Q000187:drug effects / Q000201:enzymology; D019001:Nitric Oxide Synthase / Q000096:biosynthesis / Q000235:genetics*; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012334:RNA, Neoplasm / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D014407:Tumor Cells, Cultured; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics*
D000970:Antineoplastic Agents; D017931:DNA Primers; D012333:RNA, Messenger; D012334:RNA, Neoplasm; D014409:Tumor Necrosis Factor-alpha; D019001:Nitric Oxide Synthase; D002945:Cisplatin