Combination effects of capecitabine, irinotecan and 17-AAG on colorectal cancer cell line (HT-29)

Abstract

ObjevtiveEvasion of apoptosis is a major feature of cancer cells, therefore designing treatment strategies to target apoptotic pathways seems effective. In this study, we investigate the effect of 17-AAG (17-allylaminogeldanamycin) alone and in double and triple combination with capecitabine (Cap) and irinotecan (IR) on HT-29 colon cancer cell line apoptosis. MethodsCapase-3, 8, 9, p53 and NF-κB genes expression were analyzed by Real-time PCR. DNA laddering assay was performed to confirm Real-time PCR results. ResultsOur results showed that all single treatment groups elevated expression of caspase-3, 8, and 9 significantly and IR/Cap was the only double combination group that could upregulate caspase-8 and -9. NF-κB was down-regulated in single treatment and IR/Cap double combination group, significantly. 17-AAG mono-treatment and IR/Cap and Cap/17-AAG double combination group significantly upregulated p53 gene expression. ConclusionOur findings showed proapoptotic effects of 17-AAG alone and in combination with Cap and IR. These findings propose 17-AAG in combination with routine chemotherapy, as a new protocol for colorectal cancer combination therapy.