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Synergistic effects of geldanamycin and antitumor drugs.
Liao, Z Y; Zhang, S H; Zhen, Y S.
Afiliación
  • Liao ZY; Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, China.
Yao Xue Xue Bao ; 36(8): 569-75, 2001 Aug.
Article en En | MEDLINE | ID: mdl-12579931
AIM: To study the effect of geldanamycin (GDM) on cell-cycle of human hepatoma BEL-7402 cells and the antitumor activity of cisplatin and mitomycin C in combination with GDM in vitro and in vivo. METHODS: MTT assay was used to determine the growth inhibition of hepatoma BEL-7402 cells. Cell cycle was analyzed by flow cytometry. Transplantable murine hepatoma 22 model was used to evaluate the antitumor activity of drugs in vivo. RESULTS: The IC50 value of GDM for hepatoma BEL-7402 cells by MTT assay was found to be 0.28 mumol.L-1. At concentrations of 0.1, 1.0, and 10 mumol.L-1, GDM reduced the proportion of S phase and induced G2/M arrest in BEL-7402 cells. At relatively low cytotoxic concentration, 0.1 or 0.2 mumol.L-1, GDM markedly potentiated the cytotoxicity of a series of chemotherapeutic agents including cisplatin, mitomycin C, adriamycin and cytarabine against BEL-7402 cells. The inhibition of tumor growth by cisplatin and mitomycin C was also enhanced in transplantable hepatoma 22-bearing mice when these agents were administered in combination with GDM 0.38 mg.kg-1. The synergistic effects were very significant with CDI < 0.7. CONCLUSION: These results suggest that GDM, as a biochemical modulator targeting Hsp90 function, may be potentially useful in cancer chemotherapy.
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Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Quinonas / Protocolos de Quimioterapia Combinada Antineoplásica / Antibióticos Antineoplásicos Límite: Animals Idioma: En Revista: Yao Xue Xue Bao Año: 2001 Tipo del documento: Article País de afiliación: China Pais de publicación: China
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Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Quinonas / Protocolos de Quimioterapia Combinada Antineoplásica / Antibióticos Antineoplásicos Límite: Animals Idioma: En Revista: Yao Xue Xue Bao Año: 2001 Tipo del documento: Article País de afiliación: China Pais de publicación: China