Establishment of a novel human cell line retaining the characteristics of the original pancreatic adenocarcinoma, and evaluation of MEK as a therapeutic target

Pancreatic cancer is a lethal solid malignancy with limited therapeutic options. The development of novel therapeutic drugs requires adequate new cell line models. A new pancreatic cancer cell line, designated PDXPC1, was established from one pancreatic ductal adenocarcinoma (PDAC) patientderived xenograft. The PDXPC1 cells were stably cultured for >2 years and had a stable short tandem repeat profile. The PDXPC1 cell line retained the key mutations of the primary tumor, along with the epithelial origin and other important protein expression. The PDXPC1 cells induced rapid in vivo tumor growth, both subcutaneously and orthotopically, in a mouse model with an elevated CA199 level. The PDXPC1 cells showed weak growth, invasion and migration potency compared to another pancreatic cancer cell line, but were relatively resistant to multiple anticancer drugs. Interestingly, the MEK inhibitor trametinib significantly inhibited the proliferation of PDXPC1 cells, and not that of Panc1 cells, by inactivating MEK/ERK/MYC signaling and activating the apoptotic pathway via Bcl2 degradation. In conclusion, the PDXPC1 cell line, capturing the major characteristics of the primary tumor, may be a suitable tool for studying the underlying mechanisms of chemoresistance in PDAC and developing new targeted therapeutic options.