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Antisense oligonucleotides to gastrin inhibit growth of human pancreatic cancer

J P Smith1, M F Verderame, I S Zagon

  • 1Department of Medicine, The Milton S. Hershey Medical Center, Pennsylvania State University 17033, USA.

Cancer Letters
|March 17, 1999
PubMed

Insights

Antisense oligonucleotides targeting gastrin significantly inhibited human pancreatic cancer growth in vitro and in vivo. This suggests gastrin plays a key role in pancreatic cancer progression and may be a therapeutic target.

Area of Science:

  • Oncology
  • Molecular Biology
  • Gastroenterology

Background:

  • Human pancreatic cancer growth is stimulated by autocrine gastrin production.
  • Gastrin acts as a growth factor in pancreatic cancer.
  • Targeting gastrin signaling is a potential therapeutic strategy.

Purpose of the Study:

  • To evaluate the efficacy of antisense oligonucleotides against gastrin in inhibiting pancreatic cancer growth.
  • To assess the role of gastrin in pancreatic cancer proliferation in vitro and in vivo.

Main Methods:

  • BxPC-3 human pancreatic cancer cells were treated with varying concentrations of antisense oligonucleotides to gastrin in vitro.
  • Cellular proliferation was measured using a proliferation assay.
  • Nude mice bearing BxPC-3 xenografts were treated with intratumoral injections of anti-gastrin oligonucleotides or control sequences in vivo.

Main Results:

  • In vitro, anti-gastrin oligonucleotides inhibited cancer cell growth by up to 88% in a dose-dependent manner.
  • In vivo, tumors in mice treated with anti-gastrin oligonucleotides were significantly smaller in volume and weight.
  • Gastrin levels were reduced in tumors treated with anti-gastrin oligonucleotides.

Conclusions:

  • Gastrin is a significant stimulatory peptide for human pancreatic cancer growth.
  • Antisense oligonucleotides targeting gastrin demonstrate therapeutic potential for pancreatic cancer.
  • Further investigation into gastrin-targeted antisense therapy for pancreatic cancer is warranted.

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