摘要
目的研究和探讨力达霉素对碱性成纤维细胞生长因子(bFGF)诱导的癌细胞中信号转导的抑制作用。方法MTT法检测LDM和阿霉素(ADR)对3种人癌细胞系的增殖抑制作用。受体结合实验检测LDM对bFGF与其受体结合的作用。W estern b lotting检测bFGF受体复合物的形成,流式细胞测定细胞内Ca2+的流动,免疫印迹法测定bFGF所诱导的3种PKC亚型的活性。结果MTT法实验结果,LDM在体外对3种人癌细胞均显示出强烈的增殖抑制作用。按IC50值进行比较表明,LDM的活性比ADR强1 000倍以上。LDM抑制[125I]-bFGF对大鼠肺细胞膜受体的IC50为2.0×10-4nmol.L-1。LDM能阻碍bFGF与其受体复合物的形成,LDM(10 nmol.L-1)预孵育2 h可阻止bFGF诱导的细胞内Ca2+效应。免疫印迹法证明,LDM可抑制bFGF诱导的癌细胞的3种PKC亚型的活性。结论力达霉素抗肿瘤作用的机制之一可能是通过阻断bFGF受体的信号转导途径。
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 Ca^2＋ 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.
出处
《药学学报》
CAS
CSCD
北大核心
2005年第12期1110-1115,共6页
Acta Pharmaceutica Sinica
基金
NationalKeyBasicResearchDevelopmentProgramFoundationofChina(G1998051212)
NationalFoundationforCancerResearch(USA)
