Growth inhibitory effect of celecoxib and rofecoxib on human colorectal carcinoma cell lines

Anticancer Res. 2005 Jan-Feb;25(1A):225-33.

Abstract

Background: Epidemiological studies have revealed a protective effect of NSAIDs, which principally target cyclooxygenase (COX)-1 and COX-2, on the development of colorectal cancer. Increased expression of COX-2 was shown in colorectal adenocarcinoma. However, some effects were shown to be COX-independent. Here, we compared two selective COX-2 inhibitors for their effect on the growth of colorectal tumour cells in vitro.

Materials and methods: Fifteen tumour cell lines were characterized for COX-1 and COX-2 expression by Western blot and RT-PCR. The effect of celecoxib and rofecoxib on their growth was assessed by staining of DNA with crystal violet.

Results: COX-2 expression varied among cell lines, whereas COX-1 was always expressed. Rofecoxib displayed a limited dose-related effect on cell proliferation, whereas celecoxib strongly inhibited cell growth at high concentrations. Both effects appeared COX-2-independent.

Conclusion: Rofecoxib, which is devoid of apoptotic effect at high concentration but efficient at pharmacological concentrations, revealed a potential new mechanism of action of NSAIDs towards colorectal cancer.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Caco-2 Cells
  • Celecoxib
  • Cell Proliferation / drug effects
  • Colorectal Neoplasms / drug therapy*
  • Colorectal Neoplasms / pathology
  • Cyclooxygenase 1
  • Cyclooxygenase 2
  • Cyclooxygenase 2 Inhibitors
  • Cyclooxygenase Inhibitors / pharmacology*
  • HT29 Cells
  • Humans
  • Lactones / pharmacology*
  • Membrane Proteins
  • Phenotype
  • Prostaglandin-Endoperoxide Synthases / biosynthesis
  • Prostaglandin-Endoperoxide Synthases / genetics
  • Pyrazoles / pharmacology*
  • RNA, Messenger / biosynthesis
  • RNA, Messenger / genetics
  • Reverse Transcriptase Polymerase Chain Reaction
  • Sulfonamides / pharmacology*
  • Sulfones / pharmacology*

Substances

  • Cyclooxygenase 2 Inhibitors
  • Cyclooxygenase Inhibitors
  • Lactones
  • Membrane Proteins
  • Pyrazoles
  • RNA, Messenger
  • Sulfonamides
  • Sulfones
  • rofecoxib
  • Cyclooxygenase 1
  • Cyclooxygenase 2
  • PTGS1 protein, human
  • PTGS2 protein, human
  • Prostaglandin-Endoperoxide Synthases
  • Celecoxib