Adenovirus-mediated wt-p16 reintroduction induces cell cycle arrest or apoptosis in pancreatic cancer

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Published on: November 19, 2019

J Calbó1, M Marotta, M Cascalló

  • 1Department of Biochemistry and Molecular Biology, University of Barcelona, Barcelona, Spain.

Cancer Gene Therapy
|November 1, 2001
PubMed

Insights

Gene replacement therapy using p16 (inhibitor of cyclin-dependent kinases CDK4/CDK6) shows promise for pancreatic cancer. Overexpressing p16 reduced tumor cell proliferation and inhibited tumor growth in vivo.

Area of Science:

  • Oncology
  • Molecular Biology
  • Genetics

Background:

  • Pancreatic cancer has a poor prognosis, necessitating novel therapeutic strategies.
  • Inactivation of the p16 (INK4a/CDKN2) tumor suppressor gene is a frequent event in pancreatic cancer.
  • p16 inhibits cyclin-dependent kinases CDK4 and CDK6, making it a target for gene therapy.

Purpose of the Study:

  • To investigate the therapeutic potential of p16 gene replacement in pancreatic cancer.
  • To evaluate the effects of p16 overexpression on pancreatic cancer cell lines and xenografts.

Main Methods:

  • Transfection of human pancreatic tumor cell lines (NP-9, NP-18, NP-29, NP-31) with a recombinant adenovirus carrying wt-p16 cDNA (Ad5RSV-p16).
  • Assessment of cell proliferation, G1 arrest, senescence, and apoptosis.
  • Evaluation of tumor growth inhibition in subcutaneous pancreatic xenografts.

Main Results:

  • p16 overexpression decreased proliferation in all tested pancreatic cancer cell lines.
  • G1 arrest and senescence were observed in three cell lines, while one exhibited increased apoptosis.
  • Differential cellular responses may correlate with E2F-1 expression levels.
  • In vivo experiments confirmed p16's effectiveness in inhibiting pancreatic tumor growth.

Conclusions:

  • p16 gene replacement is a promising therapeutic approach for pancreatic cancer.
  • The study highlights the potential of targeting the p16 pathway for improved treatment outcomes.

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