Intrinsic gemcitabine resistance in a novel pancreatic cancer cell line is associated with cancer stem cell-like phenotype

Pancreatic ductal adenocarcinoma (PDA) remains one of the most lethal malignanciesin the world, often diagnosed at an advanced stage, resistant to conventionalchemotherapy and having high invasive and metastatic potential. The mechanismof drug resistance of PDA is still not clear. In the present study, we establishedtwo novel pancreatic cancer cell lines PAXC-002 and PAXC-003 from human primaryxenograft models. The cell lines were characterized by morphology, karyotype,pancreatic cancer marker and short tandem repeat (STR) analysis, and growth kineticsand tumorigenicity. The in vitro anti-proliferation test revealed that PAXC-002cell was intrinsically resistant to the standard of care chemotherapy-gemcitabine,compared with that of PAXC-003 and other widely used pancreatic cancer cell lines.Interestingly, the gemcitabine resistant PAXC-002 cell line was more potent informing colonies in 3-Dimensional matrigel culture conditions and had a higherpercentage of CD133 positive cells, which is recognized as a cancer stem cellmarker, compared to the gemcitabine-sensitive PAXC-003 cell line. In this study,we present two novel pancreatic cancer cell lines which could be used for gemcitabineresistance investigation, mechanism identification of pancreatic cancer and anticancerdrug screening. The preliminary data indicate that the drug resistance of pancreaticcarcinoma cells is associated with a cancer stem cell-like phenotype.