Mechanisms underlying aspirin-mediated growth inhibition and apoptosis induction of cyclooxygenase-2 negative colon cancer cell line SW480

World J Gastroenterol. 2008 Jul 14;14(26):4227-33. doi: 10.3748/wjg.14.4227.

Abstract

Aim: To investigate the effects of aspirin (acetylsalicylic acid) on proliferation and apoptosis of colorectal cancer cell line SW480 and its mechanism.

Methods: Cyclooxygenase (COX)-2 negative colorectal cancer cell line SW480 was treated with aspirin at concentrations of 2.5 mmol/L, 5.0 mmol/L, 10.0 mmol/L for different periods in vitro. Anti-proliferation effect of aspirin on SW480 was detected by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Cell cycle and apoptosis were observed by flow cytometry (FCM). Transmission electron microscope (TEM) was used for morphological study. Apoptosis-associated genes were detected by immunohistochemical staining and Western blotting.

Results: Aspirin inhibited SW480 proliferation and induced apoptosis in a dose- and time-dependent manner. Treatment with different concentrations of aspirin significantly increased the proportions of cells at the G(0)/G(1)phase and decreased the proportions of cells at the S- and G(2)/M phases in a concentration-dependent manner. Aspirin not only induced apoptosis but also caused cell necrosis at a high concentration as well. After treatment with aspirin, SW480 cells displayed typically morphological features of apoptosis and necrosis under TEM, and increased the Bcl-2 expression in cells, but the expression of Bax was down regulated.

Conclusion: Aspirin inhibits proliferation and induces apoptosis of SW480 cells. Its anti-tumor mechanism may arrest cell cycle and shift Bax/Bcl-2 balance in cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Apoptosis / drug effects*
  • Aspirin / pharmacology*
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Colonic Neoplasms / drug therapy*
  • Colonic Neoplasms / enzymology
  • Colonic Neoplasms / pathology
  • Cyclooxygenase 2 / analysis*
  • G1 Phase / drug effects
  • Humans
  • Proto-Oncogene Proteins c-bcl-2 / analysis
  • Resting Phase, Cell Cycle / drug effects
  • bcl-2-Associated X Protein / analysis

Substances

  • Proto-Oncogene Proteins c-bcl-2
  • bcl-2-Associated X Protein
  • Cyclooxygenase 2
  • PTGS2 protein, human
  • Aspirin