Sensitivity to drugs of chemotherapy of cancer stem cells of human pancreatic carcinoma

Abstract

Objective To explore the sensitivity of cancer stem cells to chemotherapy in human pancreatic carcinoma.Methods PANC-1 ceils were cultured in an incubator filled with 5％ CO2 at a temperature of 37℃,and were labeled with Hoechst 33342.The SP analysis and sorting were performed using a FACSVantage SE.RT-PCR was performed to detect the expression of human CD133 ABCG2 and Notch1.SP and non-SP cells from the PANC-1 cell line were treated with 5-fluorouracil (5-FU; 1,10,or 100 μg/ml) or gemcitabine (10,100,or 1000μg/ml),and the cell viability was determined using the MTT assay.The sensitivity of sorted tumor cells to chemotherapeutics was determined in NOD/SCID mice model.Results SP cells were found to have higher drug-resistance both in vivo and in vitro and higher levels of mRNA expression for CD133,ABCG2 and Notch1,when compared to non-SP ceils.The xenografted tumors derived from injected SP cells and treated with gemcitabine had more CD133± cells than the untreated group.Conclusions The SP of PANC-1 pancreatic carcinoma cells are enriched with highly gemcitabine-resistant CSCs and determine the carcinogenesis of the PANC-1 pancreatic carcinoma cells. Key words: Pancreatic carcinoma; Stem cell; Drug resistance