Inhibition of telomerase activity with hTERT antisense increases the effect of CDDP-induced apoptosis in myeloid leukemia.

Abstract

As reported previously, inhibition of telomerase activity with hTERT (human telomerase reverse transcriptase) mRNA AS PS-ODN (Antisense phosphorothioate oligodeoxynucleotide) could increase the effect for CDDP (cis-diamminedichloroplatinum, CDDP) to induce apoptosis of HL-60 and K562 leukemic cells. In these studies, this phenomenon will be further investigated and expanded to leukemia cells from acute and chronic myeloid leukemia (AML and CML). Cell samples of AML and CML patients, from the first affiliated hospital of Jinan University Medical College, were obtained. The primary cell culture was established to investigate whether or not the inhibition of telomerase activity with hTERT mRNA AS PS-ODN increased the effect for cisplatin to induce apoptosis of leukemic cells from patients. Cell growth was observed with trypan blue dye exclusion. hTERT protein was determined by tissue chemistry and flowcytometry. Telomerase activity was tested with the telomerase PCR ELISA assay kit (Boehringer Mannheim). The inhibition of telomerase activity with hTERT mRNA AS PS-ODN could significantly increase the susceptibility of AML or CML cells to CDDP. The apoptotic percentage of cells (AML: 42.68%; CML: 35.72%) treated with AS PS-ODN/CDDP was significantly different from that of cells (AML, 29.02%; CML, 23.84%) treated with S PS-ODN/CDDP or CDDP. The inhibition of telomerase activity with hTERT mRNA AS PS-ODN could increase the effect for CDDP to induce apoptosis of leukemic cells from AML and CML patients.