Survivin associates with cell proliferation in renal cancer cells: regulation of survivin expression by insulin-like growth factor-1, interferon-gamma and a novel NF-kappaB inhibitor.
Although survivin has been widely recognized as an attractive target for cancer therapy, the exact mechanism regarding the regulation of survivin and its effect on cell proliferation have yet to be clearly defined in renal cell carcinoma (RCC). We investigated herein the association between survivin expression and cell proliferation in a RCC cell line, KU19-20. In KU19-20 cells, cell proliferation and survivin expression were significantly induced by IGF-1, whereas they were inhibited by a novel NF-kappaB inhibitor dehydroxymethyl-epoxyquinomicin (DHMEQ) and IFN-gamma. The combination of DHMEQ and IFN-gamma inhibited cell proliferation synergistically with a pronounced attenuation of survivin expression. Furthermore, treatment with survivin-specific siRNA reduced expression of survivin and significantly inhibited cell proliferation. Survivin expression was thus associated with cell proliferation in KU19-20 cells. The regulation of survivin by IFN-gamma and/or an NF-kappaB inhibitor may therefore be a potential treatment modality for RCC.
Sato
Akinori
A
Department of Urology, School of Medicine, Keio University, Tokyo 160-8582, Japan.
Oya
Mototsugu
M
Ito
Keiichi
K
Mizuno
Ryuichi
R
Horiguchi
Yutaka
Y
Umezawa
Kazuo
K
Hayakawa
Masamichi
M
Murai
Masaru
M
D001549:Benzamides / Q000494:pharmacology; D002292:Carcinoma, Renal Cell / Q000235:genetics / Q000473:pathology / Q000503:physiopathology; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects*; D003512:Cyclohexanones / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D051034:Inhibitor of Apoptosis Proteins; D007334:Insulin-Like Growth Factor I / Q000494:pharmacology; D007371:Interferon-gamma / Q000494:pharmacology; D007680:Kidney Neoplasms / Q000235:genetics / Q000473:pathology / Q000503:physiopathology; D008869:Microtubule-Associated Proteins / Q000235:genetics* / Q000502:physiology; D016328:NF-kappa B / Q000037:antagonists & inhibitors; D009363:Neoplasm Proteins / Q000235:genetics* / Q000502:physiology; D034622:RNA Interference / Q000502:physiology; D034741:RNA, Small Interfering / Q000235:genetics; D000077022:Survivin; D014162:Transfection
C107489:BIRC5 protein, human; D001549:Benzamides; D003512:Cyclohexanones; D051034:Inhibitor of Apoptosis Proteins; D008869:Microtubule-Associated Proteins; D016328:NF-kappa B; D009363:Neoplasm Proteins; D034741:RNA, Small Interfering; D000077022:Survivin; C464444:dehydroxymethylepoxyquinomicin; D007334:Insulin-Like Growth Factor I; D007371:Interferon-gamma