CYP3A gene variability and cancer cells response to the treatment.

Abstract

The treatment of cancer depends on the activity of the cytochrome P450 enzyme family, which is essentially carried out by the CYP3A4 and CYP3A5 enzymes. The aim of our study was to investigate whether the CYP3A4 polymorphism could contribute to protein activity and their influence to the response of cancer cells to treatment. The variability of CYP3A4 cDNA profiles between the cancer cell lines parental HT-29 and resistant HT-29-OxR adenocarcinoma was detected using denaturing gradient gel electrophoresis (DGGE). Subsequently, sequence analysis of CYP3A family members (CYP3A4, CYP3A5) confirmed polymorphism of the CYP3A4 gene in studied cancer cell lines. Variations at the gene expression level, the protein level and the activity of CYP3A4 protein in 12 cancer cell lines were observed, also different response to drug treatments between cell line HT-29 and oxaliplatin-resistant cell line HT-29-OxR. The variability of CYP3A might affect the efficiency of anti-cancer drugs in general and have an impact on metabolism.