Effect of bcl-2 antisense oligodeoxynucleotides on drug sensitivity of leukemic cells.
BACKGROUND
We investigated the effect of two antisense oligodeoxynucleotides, previously selected with the help of computer-aided RNA structure prediction, on drug sensitivity, bcl-2 expression and apoptosis of leukemia cells. The drugs tested were etoposide (VP-16), cytarabine (Ara-C), daunorubicin (DNR) and arsenic trioxide (As(2)O(3)).


METHODS
The experimental assays were performed with cultures, IC(50) of leukemic cells to drugs, immunochemistry and flow cytometry.


RESULTS
The results showed that the two antisense oligodeoxynucleotides significantly reduced IC(50) levels for VP-16, Ara-c, DNA and As(2)O(3), inhibited bcl-2 gene expression and induced apoptosis of leukemic cells.


CONCLUSIONS
Computational prediction of antisense efficacy is faster than other methods and more cost-efficient. This could hasten the development of sequences for both research and clinical applications.
Zhang
Yuan
Y
Institute of Hematology, Medical College of Jinan University, Guangzhou 510632, People's Republic of China. tzyuan@jnu.edu.cn
Lei
Xiao Yong
XY
D000971:Antineoplastic Combined Chemotherapy Protocols / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D004353:Drug Evaluation, Preclinical; D004347:Drug Interactions; D019008:Drug Resistance, Neoplasm; D005434:Flow Cytometry; D018922:HL-60 Cells; D006801:Humans; D020128:Inhibitory Concentration 50; D020014:K562 Cells; D007938:Leukemia / Q000188:drug therapy* / Q000473:pathology; D020319:Oligodeoxyribonucleotides, Antisense / Q000494:pharmacology*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000032:analysis / Q000187:drug effects / Q000235:genetics*
D020319:Oligodeoxyribonucleotides, Antisense; D019253:Proto-Oncogene Proteins c-bcl-2