Aim: To establish a pancreatic cancer stem cell model using human pancreatic cancer cells in nude mice toprovide a platform for pancreatic cancer stem cell research. Materials and
Methods: To establish pancreaticcancer xenografts using human pancreatic cancer cell line SW1990, nude mice were randomly divided into controland gemcitabine groups. When the tumor grew to a volume of 125mm3, they treated with gemcitabine at a doseof 50mg/kg by intraperitoneal injection of 0.2ml in the gemcitabine group, while the mice in control group weretreated with the same volume of normal saline. Gemcitabine was given 2 times a week for 3 times. When themodel was established, the proliferation of pancreatic cancer stem cells was observed by clone formation assay,and the protein and/or mRNA expression of pancreatic stem cell surface markers including CD24, CD44, CD133,ALDH, transcription factors containing Oct-4, Sox-2, Nanog and Gli, the key nuclear transcription factor in SonicHedgehog signaling pathway was detected by Western blot and/or RT-PCR to verify the reliability of this model.
Results: This model is feasible and safe. During the establishment, no mice died and the weight of nude micemaintained above 16.5g. The clone forming ability in gemcitabine group was stronger than that of the controlgroup (p<0.01). In gemcitabine group, the protein expression of pancreatic cancer stem cell surface markersincluding CD44, and ALDH was up-regulated, the protein and mRNA expression of nuclear transcription factorincluding Oct-4, Sox-2 and Nanog was also significantly increased (P<0.01). In addition, the protein expressionof key nuclear transcription factor in Sonic Hedgehog signaling pathway, Gli-1, was significantly enhanced(p<0.01).
Conclusions: The pancreatic cancer stem cell model was successfully established using human pancreaticcancer cell line SW1990 in nude mice. Gemcitabine could enrich pancreatic cancer stem cells, simultaneouslyaccompanied by the activation of Sonic Hedgehog signaling pathway.