Effects Of Topotecan On Proliferation And Apoptosis Of HL-60 Cells

Aim: DNA topoisomerase â…  , the important intro-nuclear enzyme, participate in series of key steps of genetic events, such as replication, transcription, recombination and repair of DNA in eukaryotic cells. It is a new target in the development of new anti-tumor drugs. Topotecan (TPT), a semisynthetic water-soluble derivative of camptothecin, is a potent inhibitor of DNA topoisomerase I. It can form trimer with Topo I and DNA that interrupt the transcription and translation of DNA, and exert an anti-tumor effect. Due to this mechanism, TPT has been applied broadly in the treatment of malignant diseases of blood system. Oncogene c-myc is a member of myc family, and the phosphate-protein encoded by this gene belongs to nuclear protein. C-myc has an important role on the proliferation, differentiation and apoptosis of normal cells. Studies revealed a high level expression of c-myc in the HL-60 cells and in leukemia cells. Experiments confirmed that the expression of c-myc could induce the apoptosis and suppress the proliferation of cells. These suggest that c-myc plays a role in the occurrence, development and prognosis of leukemia. Till now, there is little knowledge on molecular path way of TPT, although the evident anti-tumor effect of TPT on the leukemia has been observed in the clinical settings. In addition, the effect of TPT on leukemia and the relationship between TPT and c-myc gene expression remain to be investigated. The present study evaluated the effects of TPT on the induction of apoptosis of leukemia cells and the regulation of c-myc in mRNA and protein level. The study will provide data on the molecular path...