Abstract
The first-line chemotherapies for patients with unresectable pancreatic cancer (PC) are 5-fluorouracil (5-FU) and gemcitabine therapy. However, due to chemoresistance the prognosis of patients with PC has not been significantly improved. Mitochondria are essential organelles in eukaryotes that evolved from aerobic bacteria. In recent years, many studies have shown that mitochondria play important roles in tumorigenesis and may act as chemotherapeutic targets in PC. In addition, according to recent studies, mitochondria may play important roles in the chemoresistance of PC by affecting apoptosis, metabolism, mtDNA metabolism, and mitochondrial dynamics. Interfering with some of these factors in mitochondria may improve the sensitivity of PC cells to chemotherapeutic agents, such as gemcitabine, making mitochondria promising targets for overcoming chemoresistance in PC.
Highlights
Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Department of Biotechnology and Bioscience, University of Milano Bicocca, 20126 Milano, Italy; Department of Nuclear Medicine, Peking Union Medical College Hospital, Chinese Academy of Medical
The metabolic characterization of a pancreatic cancer (PC)-resistant cell line (GR-Patu8988) generated after treatment with a high dose of gemcitabine indicated that these cells, showing features of CSCs and expressing different epithelial–mesenchymal transition (EMT) markers [165,166], are characterized by enhanced glycolytic flux and a reduction in intracellular reactive oxygen species (ROS) levels, which in turn negatively regulates the expression of doublecortin-like kinase 1 (DCLK1), a newly identified CSC marker critical for the maintenance of stemness and the EMT phenotypes in PC cells [167]
It has been shown that the inhibition of NAF-1 in PC cells causes an inhibition of PC stem cell characteristics and their ability to invade, demonstrating the important role of NAF-1 in tumor progression [181]
Summary
Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliations. The exocrine function of the pancreas is executed by acinar and duct cells that produce digestive enzymes and deliver enzymes into the duodenum [1] These cells compose the vast majority of pancreatic tissue. Gemcitabine can induce the epithelial–mesenchymal transition (EMT), activate prosurvival signaling pathways, change cellular metabolism, and enhance cancer cell DNA repair mechanisms [15,16,17]. These mechanisms may participate in the onset of gemcitabine resistance in PC. The mechanisms of chemoresistance in PC are still not fully explained, but according to recent studies, mitochondria may play important roles in the chemoresistance of PC
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