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


METHODS
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).


RESULTS
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.


CONCLUSIONS
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.
Yuan
Zhang
Z
Institute of Hematology, Medical College of Jinan University, Guangzhou 510632, P.R. China. tzyuan@jnu.edu.cn
Mei
He Dong
HD
D000208:Acute Disease; D017209:Apoptosis / Q000187:drug effects; D002945:Cisplatin / Q000494:pharmacology / Q000627:therapeutic use*; D004268:DNA-Binding Proteins; D019008:Drug Resistance, Neoplasm; D004357:Drug Synergism; D004797:Enzyme-Linked Immunosorbent Assay; D005434:Flow Cytometry; D006801:Humans; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000473:pathology*; D007951:Leukemia, Myeloid / Q000473:pathology*; D009363:Neoplasm Proteins / Q000037:antagonists & inhibitors* / Q000235:genetics; D020319:Oligodeoxyribonucleotides, Antisense / Q000235:genetics / Q000627:therapeutic use*; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000235:genetics; D012334:RNA, Neoplasm / Q000235:genetics; D019098:Telomerase / Q000037:antagonists & inhibitors* / Q000235:genetics*; D013873:Thionucleotides / Q000235:genetics / Q000627:therapeutic use*; D014407:Tumor Cells, Cultured / Q000187:drug effects
D004268:DNA-Binding Proteins; D009363:Neoplasm Proteins; D020319:Oligodeoxyribonucleotides, Antisense; D012333:RNA, Messenger; D012334:RNA, Neoplasm; D013873:Thionucleotides; D019098:Telomerase; D002945:Cisplatin