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Introduction
Pancreatic cancer is a common digestive malignant tumor with low resection rate, high mortality rate and poor prognosis, as the characteristics of this tumor are masked. Pancreatic cancer patients who cannot undergo surgery are subjected to chemotherapy as a fundamental treatment modality; this modality is also a key component of systemic therapy (1). In pancreatic cancer chemotherapy, gemcitabine (GEM) was initially recommended as a first-line drug by the Food and Drug Administration (USA) in 1997. Since then, research on combination chemotherapies, such as cytotoxic drugs [5-fluorouracil (2), cisplatin (3) and capecitabine (4)] and biological agents [erlotinib (5), cetuximab (6) and bevacizumab (7)], as second-line modes of chemotherapy has been extensively conducted. Although GEM is currently the preferred drug for single chemotherapeutic applications in pancreatic cancer, the inherent and acquired resistance of cancer cells to GEM prevents the efficient improvement of the clinical benefit and survival of patients. Furthermore, the efficiency of this treatment is very low (12%) (8); as such, this drawback should be resolved in clinical applications. However, related studies have shown that the prognosis of pancreatic cancer in the past 10 years has remained unchanged.
The resistance to GEM is induced by several factors. Although numerous mechanisms have been presented, the main mechanism remains unclear. This resistance is affected by several key molecular factors, including deficiencies in drug uptake, activation of DNA repair pathways, resistance to apoptosis, enhancement of tumor microenvironments, overexpression of signaling proteins, mutations in kinase domains, activation of alternative pathways, mutations of genes and conversion to an epithelial-mesenchymal transition-like phenotype. Hence, GEM-resistance mechanisms involved in pancreatic cancer should be investigated; furthermore, a highly efficient multi-target drug with low toxicity should be developed to synergize current chemotherapy drugs or reverse drug resistance for pancreatic cancer treatment. The present study was conducted to establish a human pancreatic cancer GEM-resistant cell line and determine its biological characteristics for future studies.
Materials and methods
Cell culture and animal feeding
Human pancreatic cancer cell line PANC-1 was purchased from the Shanghai Institute of Cell Biology, China. These cells were incubated with RPMI-1640 + 10% fetal bovine serum at 37°C in a cell incubator with 5% CO2 and then digested with 0.25% trypsinogen + 2% ethylene diaminetetra acetic acid for passage at a...