Open AccessDKK 3 blocked translocation of β‐catenin/ EMT induced by hypoxia and improved gemcitabine therapeutic effect in pancreatic cancer Bxpc‐3 cell
Author(s) -
Guo Qingqu,
Qin Wenjie
Publication year - 2015
Publication title -
journal of cellular and molecular medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.44
H-Index - 130
eISSN - 1582-4934
pISSN - 1582-1838
DOI - 10.1111/jcmm.12675
Subject(s) - pancreatic cancer , gemcitabine , cancer research , wnt signaling pathway , oncogene , cancer , ectopic expression , ca19 9 , epithelial–mesenchymal transition , cell cycle , medicine , biology , signal transduction , cell culture , metastasis , microbiology and biotechnology , genetics
The Wnt/β‐catenin signalling pathway is activated in pancreatic cancer initiation and progression. Dickkopf‐related protein 3 ( DKK 3) is a member of the human Dickkopf family and an antagonist of Wnt ligand activity. However, the function of DKK 3 in this pathway in pancreatic cancer is rarely known. We examined the expression of DKK 3 in six human pancreatic cancer cell lines, 75 pancreatic cancer and 75 adjacent non‐cancerous tissues. Dickkopf‐related protein 3 was frequently silenced and methylation in pancreatic cancer cell lines (3/6). The expression of DKK 3 was significantly lower in pancreatic cancer tissues than in adjacent normal pancreas tissues. Further, ectopic expression of DKK 3 inhibits nuclear translocation of β‐catenin induced by hypoxia in pancreatic cancer Bxpc‐3 cell. The forced expression of DKK 3 markedly suppressed migration and the stem cell‐like phenotype of pancreatic cancer Bxpc‐3 cell in hypoxic conditions through reversing epithelial–mesenchymal transition ( EMT ). The stable expression of DKK 3 sensitizes pancreatic cancer Bxpc‐3 cell to gemcitabine, delays tumour growth and augments gemcitabine therapeutic effect in pancreatic cancer xenotransplantation model. Thus, we conclude from our finding that DKK 3 is a tumour suppressor and improved gemcitabine therapeutic effect through inducing apoptosis and regulating β‐catenin/ EMT signalling in pancreatic cancer Bxpc‐3 cell.