原创力文档resveratrol inhibits growth of orthotopic pancreatic tumors through activation of foxo transcription factors白藜芦醇抑制增长的原位胰腺癌肿瘤通过foxo转录因子的激活.pdfVIP
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resveratrol inhibits growth of orthotopic pancreatic tumors through activation of foxo transcription factors白藜芦醇抑制增长的原位胰腺癌肿瘤通过foxo转录因子的激活
Resveratrol Inhibits Growth of Orthotopic Pancreatic
Tumors through Activation of FOXO Transcription
Factors
1 1¤ 2 2 1
Sanjit K. Roy , Qinghe Chen , Junsheng Fu , Sharmila Shankar , Rakesh K. Srivastava *
1 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, 2 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
Abstract
Background: The forkhead transcription factors of the O class (FOXO) play a direct role in cellular proliferation, oxidative
stress response, and tumorigenesis. The objectives of this study were to examine whether FOXOs regulate antitumor
activities of resveratrol in pancreatic cancer cells in vitro and in vivo.
Methodology/Principal Findings: Pancreatic cancer cell lines were treated with resveratrol. Cell viability, colony formation,
apoptosis and cell cycle were measured by XTT, soft agar, TUNEL and flow cytometry assays, respectively. FOXO nuclear
translocation, DNA binding and transcriptional activities were measured by fluorescence technique, gelshift and luciferase
assay, respectively. Mice were orthotopically implanted with PANC1 cells and orally gavaged with resveratrol. The
components of PI3K and ERK pathways, FOXOs and their target gene expressions were measured by the Western blot
analysis. Resveratrol inhibited cell viability and colony formations, and induced apoptosis through caspase-3 activation in
four pancreatic cancer cell lines (PANC-1, MIA PaCa-2, Hs766T, and AsPC
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