Establishment and characterization of the gemcitabine-resistant human pancreatic cancer cell line SW1990/gemcitabine

Due to its rapid progression, metastasis and resistance to chemotherapy, pancreatic cancer is one of the most malignant tumor types to affect the digestive system. Gemcitabine chemotherapy is typically the first choice of treatment for advanced pancreatic cancer; however, chemoresistance is a major obstacle to successful treatment. In order to elucidate the underlying mechanisms of gemcitabine resistance in pancreatic cancer, the drug-resistant cell line SW1990-gemcitabine (SW1990-GZ) was established using the human pancreatic cancer cell line SW1990. The IC(50), resistance index and growth of SW1990 and SW1990-GZ cells were also assessed using 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide (MTT) assays. The cellular uptake of gemcitabine in SW1990 and SW1990-GZ was measured using high performance liquid chromatography (HPLC). The protein expression of p53 was also assessed by western blot analysis. The results demonstrated that the IC(50) of SW1990 and SW1990-Gz was 0.07±0.0021 and 87.5±3.24 µg/ml, respectively, and that the resistance index ratio of SW1990-Gz was 1,250. The growth rate of SW1990-GZ cells was low compared with that of SW1990 cells. The HPLC results indicated that gemcitabine uptake was markedly reduced in SW1990-GZ cells compared with in SW1990 cells at different time points. The protein expression of p53 was significantly higher in GEM-resistant SW1990-GZ cells compared with that in SW1990 cells (P<0.01). These results suggest that a human gemcitabine-resistant pancreatic cancer cell line was successfully established, with stable and significant drug resistance. The results of the present study suggest that the decreased cellular uptake of gemcitabine may serve an important role in gemcitabine chemoresistance in SW1990-GZ cells; thus, this cell line may be used as an effective in vitro model to improve our understanding of gemcitabine-resistance in pancreatic cancer.