Background: We evaluated the HMGCoA reductase activity and LDL receptor levels in human colon cancer as well as the effects of simvastatin on in vitro cell growth and apoptosis of DLD-1 and Caco2 cell lines.
Materials and methods: HMGCoA reductase activity and LDL receptor were measured by radiochemical assay and ELISA method, respectively. Cell growth and apoptosis were evaluated by MTT-test and DNA fragmentation analysis, respectively.
Results: Higher HMGCoA reductase activity and LDL receptor levels were detected in cancer than in normal mucosa. An up-regulation of HMGCoA reductase activity was detected in left-sided tumors. Simvastatin treatment produced marked anti-proliferative and pro-aptotic effects in DLD-1. Cell growth inhibition, but no apoptosis, was also evident in Caco2 cells.
Conclusion: The cholesterol pathway is involved in colon malignant transformation. Therapeutic strategies using HMGCoA reductase inhibitors as anti-cancer compounds should also take into consideration the biological and clinical differences detected inside colon tracts.