,Antisense oligodeoxynucleotides targeting the serine/threonine kinase Pim-2 inhibited proliferation

• 作 者: Jin-ming DAI Shu-qun ZHANG Wei ZHANG Ru-xian LIN Zong-zheng JI Sheng-qi WANG
• 机 构: Beijing Institute of Radiation Medicine,Beijing 100850,China“,”Department of Oncology,the Second Hos
• 出 处: 中国药理学报（英文版）
• 发表日期: 2005年3期
• 关键词: antisense oligodeoxynucleotide Pim-2 cell proliferation DU-145

Aim: To investigate the effect of antisense oligodeoxynucleotides (ASODN) targeting Pim-2 on cell proliferation of DU-145 cells. Methods: Three ASODN targeting Pim-2 were designed and synthesized. After transfection with ASODN, cell proliferation was analyzed using an MTS [3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium, inner salt] assay. In addition, Pim-2 mRNA, protein levels, and cell cycles were examined. Results:The ASODN designed and synthesized by our laboratory significantly reduced Pim-2 mRNA level and protein content in DU-145 cells. After transfection with ASODN for 48 h, a marked reduction in cell viability was observed in DU- 145 cells in a dose-dependent manner. No remarkable apoptosis occurred in cells treated with ASODN compared with control cells. However, it should be noted that G1 phase arrest was clearly observed in ASODN-treated cells. Conclusion: ASODN targeting Pim-2 resulted in a marked reduction in DU-145 cell proliferation, and induction of G1 phase cell cycle arrest is one of the important mechanisms for ASODN to reduce cell growth. Moreover, antisense inhibition of Pim-2 expression provides a new promising therapy target for prostate cancer.