resveratrol inhibits pancreatic cancer stem cell characteristics in human and krasg12d transgenic mice by inhibiting pluripotency maintaining factors and epithelial-mesenchymal transition英文论文.pdfVIP

Resveratrol Inhibits Pancreatic Cancer Stem Cell Characteristics in Human and KrasG12D Transgenic Mice by Inhibiting Pluripotency Maintaining Factors and Epithelial-Mesenchymal Transition 1 1 2 2 3 3 Sharmila Shankar , Dara Nall , Su-Ni Tang , Daniel Meeker , Jenna Passarini , Jay Sharma , Rakesh K. Srivastava2* 1 Department of Pathology and Laboratory Medicine, The University of Kansas Cancer Center, The University of Kansas Medical Center, Kansas City, Kansas, United States of America, 2 Department of Pharmacology, Toxicology and Therapeutics, and Medicine, The University of Kansas Cancer Center, The University of Kansas Medical Center, Kansas City, Kansas, United States of America, 3 Celprogen, San Pedro, California, United States of America Abstract Background: Cancer stem cells (CSCs) can proliferate and self-renew extensively due to their ability to express anti-apoptotic and drug resistant proteins, thus sustaining tumor growth. Therefore, the strategy to eradicate CSCs might have significant clinical implications. The objectives of this study were to examine the molecular mechanisms by which resveratrol inhibits stem cell characteristics of pancreatic CSCs derived from human primary tumors and KrasG12D transgenic mice. + + + + Methodology/Principal Findings: Human pancreatic CSCs (CD133 CD44 CD24 ESA ) are highly tumorigenic and form subcutaneous tumors in NOD/SCID mice. Human pancreatic CSCs expressing high levels of CD133, CD24, CD44, ESA, and aldehyde dehydrogenase also express significantly more Nanog, Oct-4, Notch1, MDR1 and ABCG2 than normal pancreatic tissues and primary pancreatic cancer cells. Similarly, CSCs from KrasG12D mice e