The antitumor activity of recombinant antitumor antiviral protein and the associated molecular mechanism in pancreatic tumor cells

Cancer Biother Radiopharm. 2012 Sep;27(7):426-33. doi: 10.1089/cbr.2012.1166. Epub 2012 Jul 11.

Abstract

Background: Pancreatic cancer has poor prognosis and high mortality. Currently, the therapy of pancreatic cancer remains a challenge. In this study, we compared the antitumor activity of the recombinant antitumor antiviral protein (RAAP), an improved interferon, with gemcitabine, a classic chemotherapy agent used for pancreatic cancer treatment.

Methods: The proliferation of Bx-PC3 pancreatic cancer cells was evaluated by an MTT assay. Cell cycle arrest and apoptosis were evaluated by flow cytometry and annexin V-FITC/propidium iodide double staining, respectively. The expressions of matrix metalloproteinase (MMP)-2, MMP-9, caspase-3, caspase-8, and caspase-9 genes were evaluated by reverse transcription-polymerase chain reaction and the Western blot analysis. A xenograft pancreatic cancer model was established by inoculating Bx-PC3 cells into athymic nude mice. The antitumor activity of RAAP and gemcitabine was tested in the xenograft tumor model.

Results: RAAP significantly inhibited proliferation, induced cell cycle arrest, and induced apoptosis in Bx-PC3 cells in vitro and delayed tumor growth in vivo. The antitumor activity of 20 ng/mL of RAAP was a little more effective than 10 μM of gemcitabine. The antitumor activity of RAAP was associated with its role in inducing caspase-3 and caspase-8 expression as well as downregulating MMP-2 expression.

Conclusions: RAAP can effectively suppress human pancreatic cancer cell growth in vitro and in vivo. The antitumor efficacy of RAAP is similar to gemcitabine.

MeSH terms

  • Animals
  • Antineoplastic Agents / pharmacology
  • Apoptosis / drug effects
  • Cell Growth Processes / drug effects
  • Cell Line, Tumor
  • Deoxycytidine / analogs & derivatives
  • Deoxycytidine / pharmacology
  • Down-Regulation
  • Female
  • Gemcitabine
  • Humans
  • Interferons / pharmacology*
  • Mice
  • Mice, Nude
  • Pancreatic Neoplasms / drug therapy*
  • Pancreatic Neoplasms / pathology
  • Recombinant Proteins / pharmacology
  • Xenograft Model Antitumor Assays

Substances

  • Antineoplastic Agents
  • Recombinant Proteins
  • Deoxycytidine
  • Interferons
  • Gemcitabine