Relationship between single nucleotide polymorphisms in the deoxycytidine kinase gene and chemosensitivity of gemcitabine in six pancreatic cancer cell lines.

Background: Single nucleotide polymorphisms (SNPs) in the deoxycytidine kinase (dCK) gene are associated with chemosensitivity to nucleoside analogs. 2',2'-Difluoro 2'-deoxycytidine (gemcitabine) is a first-line nucleoside analog drug in the treatment of pancreatic cancer. However, the association between SNPs in the dCK gene and chemosensitivity to gemcitabine has not been fully established. Therefore, the present study aimed to investigate the relationship between SNPs in the dCK gene and chemosensitivity to gemcitabine in human pancreatic cancer cell lines.

Methods: Seven SNPs in the dCK gene were sequenced in six human pancreatic cancer cell lines. The chemosensitivity of these six cell lines to gemcitabine were evaluated in vitro with a Cell Counting Kit-8 (CCK-8) test. Inhibition rates were used to express the chemosensitivity of pancreatic cancer cell lines to gemcitabine.

Results: The genotype of the A9846G SNP in the dCK gene was determined in six human pancreatic cancer cell lines. The cell lines BxPC-3 and T3M4 carried the A9846G SNP genotype AG, whereas cell lines AsPC-1, Mia PaCa2, SW1990 and SU86.86 carried the GG genotype. Cell lines with the AG genotype (BxPC-3 and T3M4) were more sensitive to gemcitabine compared with cell lines with the GG genotype (AsPC-1, Mia PaCa2, SW1990 and SU86.86) and significantly different inhibition rates were observed between cell lines carrying the AG and GG genotypes (P < 0.01).

Conclusions: Variants in the A9846G SNP of the dCK gene were associated with sensitivity to gemcitabine in pancreatic cancer cell lines. The dCK A9846G SNP may act as a genetic marker to predict chemotherapy efficacy of gemcitabine in pancreatic cancer.