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Antisense oligonucleotides targeting midkine induced apoptosis and increased chemosensitivity in hepatocellular

Li-cheng Dai1, Xiang Wang, Xing Yao

  • 1Huzhou Key Laboratory of Molecular Medicine, Huzhou Central Hospital, Huzhou 313000, China. dlc@hzhospital.com

Acta Pharmacologica Sinica
|November 23, 2006
PubMed
Abstract

Insights

Antisense oligonucleotides targeting midkine (MK) show promise for treating hepatocellular carcinoma (HCC). A specific compound, ASODN5, effectively inhibited HCC cell growth and enhanced chemotherapy sensitivity.

Area of Science:

  • Oncology
  • Molecular Biology
  • Drug Discovery

Background:

  • Midkine (MK) is overexpressed in various cancers, including hepatocellular carcinoma (HCC).
  • Targeting MK offers a potential therapeutic strategy for HCC treatment.

Purpose of the Study:

  • To screen for effective antisense oligonucleotides (ASODN) targeting MK in HCC cells.
  • To evaluate the antitumor activity and therapeutic potential of identified ASODN.

Main Methods:

  • Ten ASODN targeting MK were designed and synthesized.
  • ASODN transfection, cell proliferation (MTS assay), MK mRNA/protein levels, apoptosis, and caspase-3 activity were analyzed in HepG2 cells.
  • Combination therapy with ASODN and chemotherapeutic drugs was assessed.

Main Results:

  • ASODN5 demonstrated significant dose-dependent inhibition of HCC cell proliferation.
  • ASODN5 effectively reduced MK mRNA and protein levels in HepG2 cells.
  • ASODN5 induced apoptosis, increased caspase-3 activity, and enhanced chemosensitivity in HCC cells.

Conclusions:

  • Antisense oligonucleotides targeting MK exhibit therapeutic effects against HCC.
  • ASODN5 shows potential as an effective antitumor agent for HCC treatment.

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