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Propofol inhibits pancreatic cancer progress under hypoxia via ADAM 8
Author(s) -
Gao Yutong,
Yu Xiangdi,
Zhang Fangxiang,
Dai Jing
Publication year - 2019
Publication title -
journal of hepato‐biliary‐pancreatic sciences
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.63
H-Index - 60
eISSN - 1868-6982
pISSN - 1868-6974
DOI - 10.1002/jhbp.624
Subject(s) - angiogenesis , chemistry , angiogenin , vascular endothelial growth factor , blot , pancreatic cancer , viability assay , propofol , hypoxia (environmental) , cell growth , cancer research , cell , pharmacology , medicine , cancer , biochemistry , vegf receptors , organic chemistry , oxygen , gene
Background To investigate the potential anti‐tumoral properties of propofol in pancreatic cancer and elucidate the underlying mechanisms. Methods The relative expression of ADAM metallopeptidase domain 8 ( ADAM 8) in response to hypoxia in Panc1 cells was analyzed by western blotting. The enzymatic activity was determined by fluorescence release from PEPDAB 013 decomposition. Cell growth was measured via cell counting and cell viability was measured using CCK ‐8 kit. Cell migrative capacity was evaluated by transwell and adhesion assay. The relative abundance of angiogenesis‐related markers including platelet‐derived growth factor AA, angiogenin, endothelin‐1 and vascular endothelial growth factor were determined by real‐time polymerase chain reaction and western blotting. The anti‐tumoral activity of propofol was investigated with Panc1‐derived xenograft mice model. Results ADAM8 was significantly induced by hypoxia and efficiently inhibited by co‐treatment with propofol. Propofol suppressed proliferation and compromised viability of Panc1 cells. In addition, the migrative capacity was greatly inhibited by propofol dosage. Comprehensive profiling of angiogenesis‐related markers demonstrated that propofol remarkably suppressed neovascularization response in Panc1 cells under hypoxia. We further uncovered that propofol administration via subcutaneous injection delayed xenograft tumor progression. Conclusion Propofol specifically inhibited ADAM 8 expression and activation in response to hypoxia in pancreatic cancer, and held great value for therapeutic effects.