Synergistic Effect of Simvastatin Plus Radiation in Gastric Cancer and Colorectal Cancer: Implications of BIRC5 and Connective Tissue Growth Factor

摘要: Purpose We investigated the synergistic effect of simvastatin, a 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor plus radiation therapy, on proliferation and survival gastric cancer (GC) colorectal (CRC) cells. We also studied several genes involved in simvastatin/radiation-induced effects. Methods Materials Gastric (AGS, SNU601, MKN1, MKN28) CRC (CoLo320, SW48, HT29, HCT8) cell lines were treated with 0.2 μM simvastatin alone, or combination 0 to 4 Gy radiation, subjected clonogenic assays in vitro. To assess molecular mechanism treatment, we performed microarray analysis, immunoblot assays, small interfering RNA knockdown experiments, plasmid rescue assays. The antitumoral effects evaluated in vivo using xenograft models. Results therapy inhibited basal GC cells Simvastatin suppressed expression BIRC5 CTGF these cells. In vivo, combined treatment significantly reduced growth tumors compared alone. Conclusion suggest that has through induction apoptosis, which may be mediated by simultaneous inhibition expression. clinical trial patients is warranted.