Study Of Echinomycin On Growth Suppression In Gleveec-sensitive And Gleveec-resistence K562 Cells

Gleveec is a novel drug for CML at present,the mechanism by which of gleveec suppresses tumor growth is to selectively inhibit Bcr-Abl, a virulence gene of CML,however,tumor resistance to gleveec is increasingly encountered in clinical patients. Therefore, it is a need to develop some novel inhibitors for CML resistance and therapy.We found a high active component from microbial metabolite of Streptomyces sp.2215,which is identified to be echinomycin, a cyclic peptide antibiotic.We evulated antitumor activity of echinomycin in gleveec-sensitive and gleveec-resistence K562 cells using MTT assay and FACS,we also further explored the mechanism by which echinomycin induced the apoptosis of the tumour cells by western-blot and RT-PCR. The results showed: 1. Echinomycin could inhibit tumor growth in gleveec-sensitive and gleveec-resistence K562 cells, its IC50 is 0.82ng/ml for gleveec-sensitive K562 cells and 0.87ng/ml for gleveec-resistence K562 cells,respectively, whereas it had a little effect on normal Vero and LO2 cells at the same dosage. 2.Echinomycin induced apoptosis of tumour cells by downregulating ERK1/2,AKT and Bcr-Abl. 3.Echinomycin could inhibit the expression of S1P,P-gp and HIF-1 in K562/Glv.These results suggested that echinomycin could selectively kill tumor cells and lead to apoptosis of tumor cells by targeting bcr-Abl and regulating AKT,ERK1/2.Echinomycin was also able to reverse the resistence of K562/Glv cells by down-regulating sphingosine phosphate-1-mediated P-glycoprotein expression. In conclution, echinomycin might be a perspective compound for tumor treatment.