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Cooperative inhibitory effects of antisense oligonucleotide of cell adhesion molecules and cimetidine on cancer cell

Nan-Hong Tang1, Yan-Ling Chen, Xiao-Qian Wang

  • 1Hepato-Biliary Surgery Institute of Fujian Province, Union Hospital, 29 Xinquan Road, Fuzhou 350001, Fujian Province, China. fztnh@sina.com

World Journal of Gastroenterology
|December 27, 2003
PubMed
Abstract

Insights

Antisense oligonucleotide (ASO) combined with cimetidine effectively reduces cancer cell adhesion to endothelial cells. This combination therapy shows stronger anti-adhesion effects than either treatment alone, offering promise for gene therapy.

Area of Science:

  • Molecular Biology
  • Cell Biology
  • Cancer Research

Background:

  • Cell adhesion molecules like E-selectin and ICAM-1 play a crucial role in tumor cell metastasis.
  • Endothelial cell activation by inflammatory signals can enhance tumor cell adhesion.

Purpose of the Study:

  • To investigate the synergistic effects of antisense oligonucleotide (ASO) targeting cell adhesion molecules and cimetidine on E-selectin and ICAM-1 expression.
  • To evaluate the impact of this combination therapy on the adhesion of tumor cells to endothelial cells in vitro.

Main Methods:

  • Endothelial cells were treated with ASO and/or cimetidine, followed by TNF-alpha induction.
  • E-selectin and ICAM-1 protein and mRNA levels were quantified using flow cytometry and RT-PCR.
  • Tumor cell adhesion to endothelial cells was assessed via cell adhesion assays.

Main Results:

  • The combination of ASO and cimetidine significantly downregulated E-selectin and ICAM-1 expression and reduced tumor cell adhesion compared to single treatments.
  • ASO targeting E-selectin, in combination with cimetidine, demonstrated the most potent inhibition of endothelial cell adhesion to tumor cells.
  • Cimetidine alone inhibited E-selectin but not ICAM-1 expression, while ASO targeting ICAM-1 showed limited impact on adhesion.

Conclusions:

  • ASO in combination with cimetidine effectively inhibits endothelial cell adhesion to cancer cells in vitro.
  • This combination therapy presents a promising strategy for anti-adhesion gene therapy in cancer treatment.
  • The findings support the development of targeted gene therapies to disrupt tumor cell metastasis.

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