Antisense oligonucleotide targeting midkine suppresses in vivo angiogenesis

Li-Cheng Dai1, Xiang Wang, Xing Yao

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

Abstract

Insights

Antisense oligonucleotide targeting midkine (MK-AS) effectively inhibits angiogenesis and hepatocellular carcinoma (HCC) growth in vivo. This study demonstrates MK-AS as a promising antiangiogenesis agent for HCC treatment.

Area of Science:

  • Oncology
  • Molecular Biology
  • Biochemistry

Background:

  • Hepatocellular carcinoma (HCC) is a prevalent cancer with significant mortality.
  • Angiogenesis, the formation of new blood vessels, is crucial for tumor growth and metastasis.
  • Midkine (MK) is a growth factor implicated in promoting angiogenesis and tumor progression in various cancers, including HCC.

Purpose of the Study:

  • To investigate the antiangiogenic potential of an antisense oligonucleotide targeting midkine (MK-AS).
  • To evaluate the efficacy of MK-AS in inhibiting angiogenesis within a chick chorioallantoic membrane (CAM) model.
  • To assess the effect of MK-AS on the growth of in situ human hepatocellular carcinoma (HCC).

Main Methods:

  • Utilized an in situ human HCC model and the chick chorioallantoic membrane (CAM) assay.
  • Assessed the impact of MK-AS on angiogenesis through cell proliferation assays.
  • Employed hematoxylin-eosin (HE) staining to evaluate histological changes and vascularization.

Main Results:

  • MK-AS significantly inhibited the proliferation of human umbilical vein endothelial cells (HUVEC) and in situ human HCC.
  • MK-AS demonstrated a suppressive effect on angiogenesis in both the HEPG2-induced CAM model and in situ human HCC tissues.
  • These findings indicate a direct role of MK-AS in modulating tumor vascularization.

Conclusions:

  • Antisense oligonucleotide targeting midkine (MK-AS) is a potent inhibitor of angiogenesis in vivo.
  • MK-AS exhibits significant anti-tumor growth effects in HCC models.
  • MK-AS represents a promising therapeutic strategy for targeting angiogenesis in hepatocellular carcinoma.

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