grape proanthocyanidin inhibit pancreatic cancer cell growth in vitro and in vivo through induction of apoptosis and by targeting the pi3kakt pathway葡萄proanthocyanidin抑制胰腺癌细胞生长在体外和体内通过诱导细胞凋亡和针对pi3kakt通路.pdfVIP

Grape Proanthocyanidin Inhibit Pancreatic Cancer Cell Growth In Vitro and In Vivo through Induction of Apoptosis and by Targeting the PI3K/Akt Pathway 2 2 1,2,3,4 Ram Prasad , Mudit Vaid , Santosh K. Katiyar * 1 Birmingham Veterans Affairs Medical Center, Birmingham, Alabama, United States of America, 2 Department of Dermatology, University of Alabama at Birmingham, Birmingham, Alabama, United States of America, 3 Nutrition Obesity Research Center, University of Alabama at Birmingham, Birmingham, Alabama, United States of America, 4 Comprehensive Cancer Center, University of Alabama at Birmingham, Birmingham, Alabama, United States of America Abstract Pancreatic cancer is an aggressive malignancy that is frequently diagnosed at an advanced stage with poor prognosis. Here, we report the chemotherapeutic effects of bioactive proanthocyanidins from grape seeds (GSPs) as assessed using In Vitro and In Vivo models. Treatment of human pancreatic cancer cells (Miapaca-2, PANC-1 and AsPC-1) with GSPs In Vitro reduced cell viability and increased G2/M phase arrest of the cell cycle leading to induction of apoptosis in a dose- and time- dependent manner. The GSPs-induced apoptosis of pancreatic cancer cells was associated with a decrease in the levels of Bcl-2 and Bcl-xl and an increase in the levels of Bax and activated caspase-3. Treatment of Miapaca-2 and PANC-1 cells with GSPs also decreased the levels of phosphatidylinositol-3-kinase (PI3K) and phosphorylation of Akt at ser473. siRNA knockdown of PI3K from pancreatic cancer cells also reduced the phosphorylation of Akt. Further, dietary administration of GSPs (0.5%, w/w) as a supplemented AIN76A control diet significantly inhibited the growth of Miapaca-2 pancreatic tumor xe