Abstract
Aim:
Overexpression of midkine (MK) has been observed in many malignancies. This aim of this study is to screen for suitable antisense oligonucleotides (ASODN) targeting MK in hepatocellular carcinoma (HCC) cells and evaluate its antitumor activity.
Methods:
Ten ASODN targeting MK were designed and synthesized. After transfection with ASODN, cell proliferation was analyzed with MTS [3 -(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium, inner salt] assay. In addition, MK mRNA, protein levels, as well as apoptosis and caspase-3 activity were also examined in HepG2 cells. Cell proliferation was then analyzed after treatment with both ASODN and chemotherapeutic drugs.
Results:
In this experiment, the ASODN5 among the 10 ASODN showed higher inhibitory activity against proliferation of hepatocellular carcinoma cells in a dose-dependent manner. In HepG2 cells, ASODN5 could significantly reduce the MK mRNA level and protein content. After transfection with ASODN5 for 48 h, accompanied with a decline of survivin and Bcl-2 protein content, a remarkable increase of apoptosis and caspase-3 activity was observed in HepG2 cells. Furthermore, ASODN5 transfer can significantly increase chemosensitivity in HepG2 cells.
Conclusion:
Antisense oligonucleotides targeting MK shows therapeutic effects on HCC; ASODN5 has the possibility to be developed as an effective antitumor agent.
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Project supported by the Zhejiang Province Medicine and Sanitation Research Foundation (2003A077).
The Editor has retracted this article because some of the figures have errors which were introduced during the process of integrating and editing the original images (Figures 3, 4, and 5). Due to the fact that the research was conducted over ten years ago, the original data can no longer be found, and the article cannot be corrected. All authors agree to this retraction.
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Dai, Lc., Wang, X., Yao, X. et al. RETRACTED ARTICLE: Antisense oligonucleotides targeting midkine induced apoptosis and increased chemosensitivity in hepatocellular carcinoma cells. Acta Pharmacol Sin 27, 1630–1636 (2006). https://doi.org/10.1111/j.1745-7254.2006.00459.x
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DOI: https://doi.org/10.1111/j.1745-7254.2006.00459.x
