Effect of BcL-2 antisense drug with different structure on the biological function of K562 cells

Chinese Journal of Cancer Research - Tập 16 - Trang 109-112 - 2004
Xiao-yong Lei1, Huan Zhang1, Dong-mei He1
1Institute of Hematology, Jinan University, Guangzhou

Tóm tắt

Objective: To study the differences and similarities of the antisense drugs with different structures on the biological functions of K562 cells. Methods: Cytotoxic effects were measured by use of a cell viability assay. Flow cytometric analysis and agarose gel electrophoresis of DNA fragmentation were also performed. The expression level of protein was assayed by immunofluorescence using fluoresce isothiocyanate label. Results: PNA targeting the coding region of the Bcl-2 messenger RNA could effectively inhibit K562 cell viability, down-regulate the synthesis of the Bcl-2 protein and increase cell apoptosis. By 72 h after the Bcl-2 antisense PNA treatment, K562 cells showed more reduction in the level of Bcl-2 protein compared with cells treated with the antisense ODN. After treatment with 10 µmol/L of Bcl-2 antisense PNA or antisense ODN for 72 h, apoptotic rates of K562 cells were 13.15±1.13 and 11.72±1.12, respectively. Furthermore, there was significant difference in the percentage of apoptotic cells between antisense PNA group and antisense ODN group. Conclusion: The results suggest that antisense PNA targeting the coding region of Bcl-2 mRNA has better antisense effects than the antisense oligonucleotides on inducing apoptosis of K562 cells.

Tài liệu tham khảo

Kirkland MA, Obrien SG, Goldman JM. Antisense therapeutics in haematological malignancies[J]. Br J Haematol 1994; 87: 447–52.

Reed JC, Stein C, Subasingle C, et al. Antisense-mediated inhibition of Bcl-2 protooncogene expression and leukemic cell growth and survival: comparisons of phosphodiester and phosphorothioate oligodeoxy-nucleotides[J]. Cancer Res 1990; 50: 6565–70.

Lei XY, Zhang H. Effect of Bcl-2 antisense oligonucleotide targeting different region of Bcl-2 mRNA on drug-sensitivity of leukemia cells[J]. Chin J Pharmacol Ther 2001; 6: 1–4.

Lei XY, Zhang H, He DM. Bcl-2 antisense oligodeoxynucelotide enhances araninosyl cytosine-induced apoptosis of primary leukemia cells[J]. Chin J Cancer 2002; 21:1301–4.

Wang J, Liu X, Jiang W. Co-transfection of MRP and Bcl-2 antisense S-oligodeoxynucleotides reduces drug resistance in cisplatin-resistant lung cancer cells[J]. Chin Med J 2000; 113: 957–60.