Lidamycin inhibits the cancer cell PKC activity induced by basic fibroblast growth factor.
Yao Xue Xue Bao
; 40(12): 1110-5, 2005 Dec.
Article
en En
| MEDLINE
| ID: mdl-16496675
AIM: To study the mechanism of inhibition of basic fibroblast growth factor (bFGF) related signal transduction by lidamycin in cancer cells. METHODS: MTT assay was used to determine the growth inhibitory effect of lidamycin (LDM) and adriamycin (ADR) in several cancer cell lines. The inhibition of bFGF bound to its receptor by LDM was measured with [125I]-bFGF binding assay. Intracellular Ca2+ stimulated by bFGF was measured by Fura-3. The formation of bFGF-receptor immune complex and the inhibitory effect of LDM on the activity of PKC isoenzymes induced by bFGF in cancer cells were identified by Western blotting analysis. RESULTS: LDM displayed extremely potent growth inhibitory effect on several cancer cell lines in a dose-dependent manner. A comparison of the IC50 values showed that the effect of LDM was 1000-fold more potent than that of ADR. LDM blocked the specific binding of [125I]-bFGF to rat lung membranes with an IC50 value of 2.0 x 10(-4) nmol x L(-1). As detected by anti-FGFR specific antibody, LDM inhibited the formation of bFGF-receptor immune complex. bFGF induced cytosolic Ca2+ response was obstructed by pretreatment with 10 nmol x L(-1) LDM. Immunoblotting demonstrated that LDM inhibited the activity of PKC isoenzymes in cancer cells stimulated with bFGF. CONCLUSION: The blocking of bFGF receptors in the signal transduction pathway may be involved in the effect of LDM on cancer cells.
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Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Proteína Quinasa C
/
Factor 2 de Crecimiento de Fibroblastos
/
Enediinos
/
Aminoglicósidos
/
Antibióticos Antineoplásicos
Tipo de estudio:
Prognostic_studies
Límite:
Animals
/
Female
/
Humans
Idioma:
En
Revista:
Yao Xue Xue Bao
Año:
2005
Tipo del documento:
Article
País de afiliación:
China
Pais de publicación:
China