Lidamycin inhibits the cancer cell PKC activity induced by basic fibroblast growth factor.

Hong-ying Zhen; Yun-hong Huang; Yong-su Zhen

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Lidamycin inhibits the cancer cell PKC activity induced by basic fibroblast growth factor.

Author: Hong-ying ZHEN ¹ ; Yun-hong HUANG ; Yong-su ZHEN
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1. Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, China. zhenys@public.bta.net.cn
Publication Type:Journal Article
MeSH: Aminoglycosides; administration & dosage; pharmacology; Animals; Antibiotics, Antineoplastic; administration & dosage; pharmacology; Breast Neoplasms; pathology; Calcium; metabolism; Cell Line, Tumor; Cell Proliferation; drug effects; Dose-Response Relationship, Drug; Doxorubicin; pharmacology; Enediynes; administration & dosage; pharmacology; Female; Fibroblast Growth Factor 2; pharmacology; HT29 Cells; Humans; Membrane Proteins; metabolism; Protein Binding; Protein Kinase C; metabolism; Rats; Receptors, Fibroblast Growth Factor; metabolism; Signal Transduction
From: Acta Pharmaceutica Sinica 2005;40(12):1110-1115
CountryChina
Language:English
Abstract:
AIMTo study the mechanism of inhibition of basic fibroblast growth factor (bFGF) related signal transduction by lidamycin in cancer cells.
METHODSMTT 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.
RESULTSLDM 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.
CONCLUSIONThe blocking of bFGF receptors in the signal transduction pathway may be involved in the effect of LDM on cancer cells.