Antisense oligodeoxynucleotides targeting the serine/threonine kinase Pim-2 inhibited proliferation of DU-145 cells

Abstract

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.

Ectopic Over-expression of Oncogene Pim-2 Induce Malignant Transformation of Nontumorous Human Liver Cell Line L02

“…Based on these findings, it was believed that ectopic overexpression of Pim-2 could induce malignant transformation of nontumorous human liver cell line L02 cells. This conclusion is supportive to our previous presumption that Pim-2 may take part in the tumorigenesis of hepatocellular carcinoma, and was in accordance with the researches on Pim-2 in lymph and hematopoiesis system tumors (8-10). …”

Antisense oligonucleotides targeting midkine induced apoptosis and increased chemosensitivity in hepatocellular carcinoma cells

“…By inducing degradation of the mRNA encoding the protein, oligonucleotides have the potential for cancer therapy [32] . The present study aims to develop potential antisense oligonucleotides (ASODN) to repress MK expression in hepatocellular carcinoma cells and examine their antiproliferation activity.…”

The over-expression of Pim-2 promote the tumorigenesis of prostatic carcinoma through phosphorylating eIF4B

“…Pim‐2 has been proved to participate in the development of lymphoma, leukemia and multiple myeloma . Recently, it is reported that Pim‐2 could enhance the invasiveness of prostatic carcinoma (PCA) cell line DU‐145 , and antisense oligonucleotide targeted at Pim‐2 could reduce the growth rate of DU‐145 cells . So it is speculated that the anti‐apoptotic effect of Pim‐2 may be associated with the development of PCA.…”