The ABCB1 3435C > T polymorphism influences docetaxel transportation in ovarian cancer

Abstract

Objective

To investigate the effect of the ATP-binding cassette transporter superfamily B member 1 gene ( ABCB1) 3435C > T single nucleotide polymorphism (SNP) on docetaxel transportation in ovarian cancer cells.

Methods

ES-2 and SKOV3 cells were transfected with an ABCB1 3435C > T recombinant plasmid, and mRNA expression was detected by real-time PCR. The MTT assay was used to detect the toxicity of docetaxel. High-performance liquid chromatography determined the drug concentration in different cell models to evaluate intracellular accumulation, and a transmembrane resistance experiment was used to assess permeability and evaluate the effect of P-gp activity on drug transportation. A tumor-bearing mouse model was established to evaluate the effect of ABCB1 3435C > T on docetaxel resistance.

Results

P-gp was overexpressed in cells transfected with the ABCB1 3435C > T plasmid, leading to a significant increase in drug resistance to docetaxel. ABCB1 3435C/wild-type transfection significantly promoted the transport of docetaxel mediated by P-gp compared with ABCB1 3435T/mutant transfection.

Conclusion

P-gp encoded by the ABCB1 variant allele appears to be more efficient at transporting docetaxel compared with the wild-type allele. The ABCB1 3435C > T SNP dramatically affected the efflux ability of P-gp against docetaxel, and may influence P-gp expression and activity.