Analysis of gene expression in gemcitabine resistant cells derived from human pancreatic cancer cell

To analyze the expression of genes involved in gemcitabine-resistant cells derived from human pancreatic cancer cell, we established several cell lines with different acquired resistance to gemcitabine from pancreatic cancer cell line MIA-PaCa2, and analyzed the expression of the genes that are considered to be associated with the resistance to gemcitabine using PCR and real-time PCR. We found that in these gemcitabine-resistant cell lines, the expression of human equilibrative nucleoside transporter 2 (hENT2) and deoxycytidine deaminase (DCTD) was lower than that of the parental cell line MIA-PaCa2 in the earlier stage of the cells incubated with 300nM gemcitabine; and, in the later stage, the expression of hENT2 recovered, but the expression levels of ribonucletide reductase subunit M1 (RRM1) and M2 (RRM2) were increased. These findings suggest that the decreased accumulation of gemcitabine and the increased expression of RRM1 and RRM2 are involved in gemcitabine-resistance formation in MIA-PaCa2.