Molecular features linked to the growth-inhibitory effects of gemcitabine on human pancreatic cancer cells

Although gemcitabine (GEM) is widely used in the treatment of pancreatic cancers, the molecular mechanisms that underlie its anti-tumor effects are not fully understood. To clarify the anti-tumor mechanism(s) of GEM, we studied a human pancreatic cancer cell line, YPK-1, that showed a 50% inhibitory concentration (IC50) of GEM of 6.3 x 10(-3) mu g/ml after 72 h of exposure. Cell proliferation was perturbed by 6 to 72 h of exposure to GEM concentrations equal to one-half or one-quarter of the IC50. We used cDNA microarrays containing 2976 genes to identify genes with expression affected by exposure to GEM. The self-organizing map identified nine clusters, including 85 and 87 genes, that showed differential expression in response to exposure to one half and one quarter IC50 GEM, respectively. Of these, 24 genes were common to cells exposed to the two different concentrations of GEM. Most are signal transduction or transcription-related genes. The microarray data for two of these genes, SPARC and RPS8, were validated by RT-PCR. Although further studies are needed to examine whether the changes in expression, profiles of these genes are specific to cells exposed to GEM, the present data provide insights into the anti-tumor effects of GEM on pancreatic cancers.