Lidamycin inhibits the cancer cell PKC activity induced by basic fibroblast growth factor
- VernacularTitle:力达霉素对碱性成纤维细胞生长因子诱导的肿瘤细胞PKC活性的抑制
- Author:
Hongying ZHEN
;
Yunhong HUANG
;
Yongsu ZHEN
- Publication Type:Journal Article
- Keywords:
lidamycin;
basic fibroblast growth factor;
signal transduction;
antitumor activity
- From:
Acta Pharmaceutica Sinica
2005;40(12):1110-1115
- CountryChina
- Language:Chinese
-
Abstract:
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 1 000-fold more potent than that of ADR. LDM blocked the specific by anti-FGFR specific antibody, LDM inhibited the formation of bFGF-receptor immune complex. bFGF 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.
