Gemcitabine (GEM) is first-line standard chemotherapy used for the treatment of pancreatic cancer; however resistance of pancreatic cancer to GEM remains the major obstacle to the successful control of this disease. Toward understanding the molecular mechanisms associated with GEM-induced resistance, here the authors developed and investigated the GEM-resistant pancreatic cancer MIA PaCa-2 cells (MIA PaCa-2/GR). the authors showed that MIA PaCa-2/GR cells underwent distinct morphological changes including spindle-shaped morphology, appearance of pseudopodia and reduced adhesion characteristic of transformed fibloblasts. the authors also found that Vimentin was up-regulated, while E-Cadherin was down-regulated in MIA PaCa-2/GR cells; these are the typical characteristics of epithelial-to-mesenchymal transition (EMT) phenotype. In addition, MIA PaCa-2/GR cells induced the expression of anti-apoptotic proteins including Survivin, XIAP and Bcl2, and activated the phosphorylation and expression of c-MET. Moreover, MIA PaCa-2/GR cells displayed higher expression level and activity of ALDHIAI, the molecular maker of cancer stem cells, emphasizing that MIA PaCa-2/GR cells increased the population of pancreatic cancer stem cells. These novel findings may lead to development of an effective therapeutic regimen to overcome the resistance of pancreatic cancer to GEM.
Lọc theo danh mục
Lượt truy cập :
20,476,194
Xem toàn văn