The Wnt/ß-catenin signaling pathway mechanism for pancreatic cancer chemoresistance in a three-dimensional cancer microenvironment.

ABSTRACT

ß-catenin is a key protein that is encoded by the CTNNB1 gene in the Wnt signaling pathway. This study investigated the associations between ß-catenin expression and implications for the efficacy of gemcitabine on pancreatic cancer cells in a three-dimensional (3-D) cancer microenvironment. For low ß-catenin expression pancreatic carcinoma cells, the inhibition rates (IRs) for low, middle, and high doses of gemcitabine were 0.615 ± 0.079, 0.691 ± 0.093, and 0.765 ± 0.061, respectively. For the high ß-catenin expression pancreatic carcinoma cells, the IRs for the same doses were 0.325 ± 0.072, 0.453 ± 0.075, and 0.537 ± 0.056, respectively. Additionally, the evaluation of ß-catenin immunoreactivity in 31 pancreatic cancer patients revealed that the low ß-catenin protein expression group had significantly longer overall survival (OS) and disease free survival (DFS) than the high ß-catenin protein group (P < 0.05). Overall, ß-catenin protein expression levels were significantly correlated to gemcitabine sensitivity in seven pancreatic carcinoma cell lines in the 3-D cancer microenvironment. These data suggest that large-scale clinical studies are warranted to assess the role of the Wnt/ß-catenin signaling pathway on ß-catenin protein expression and chemosensitivity to gemcitabine in pancreatic cancer.