LY294002 Enhances Inhibitory Effect of Gemcitabine on Proliferation of Human Pancreatic Carcinoma PANC-1 Cells

• Published in: Journal of Huazhong University of Science and Technology. Medical sciences Vol. 33; no. 1; pp. 57 - 62
• Main Author: 柯晓煜 王渝 谢祚启 刘志清 张翠芳 赵秋 杨东亮
• Format: Journal Article
• Language: English
• Published: Heidelberg Huazhong University of Science and Technology 01-02-2013; Department of Pathology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China%Department of Gastroenterology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China%Department of Infectious Diseases, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology,Wuhan 430022, China
• Subjects: Adult; Antimetabolites, Antineoplastic - administration & dosage; Cell Proliferation - drug effects; Chromones - administration & dosage; Deoxycytidine - administration & dosage; Deoxycytidine - analogs & derivatives; Dose-Response Relationship, Drug; Drug Synergism; Drug Therapy, Combination - methods; Enzyme Inhibitors - administration & dosage; Female; Humans; Male; Medicine; Medicine & Public Health; Middle Aged; Morpholines - administration & dosage; Pancreatic Neoplasms - drug therapy; Pancreatic Neoplasms - pathology; Phosphatidylinositol 3-Kinases - antagonists & inhibitors; Treatment Outcome; Tumor Cells, Cultured; Western印迹法; 抑制作用; 磷脂酰肌醇; 细胞增殖; 胰腺癌; 胰腺组织; 蛋白激酶B; 蛋白质水平; multidrug-resistance like protein; LY294002; pancreatic carcinoma; phosphorylated protein kinase B; phosphatidylinositide 3-kinase
• ISSN: 1672-0733; 1993-1352
• DOI: 10.1007/s11596-013-1071-5

Phosphatidylinositide 3-kinase （PI3K）/protein kinase B （PKB, Akt） pathway plays a major role in proliferation and survival of many types of cells. The inhibitory effect of LY294002, widely ap- plied as an inhibitor of PI3K, in combination with gemcitabine on proliferation of PANC-1 ceils was investigated. The expression of PI3K, phosphorylated AM （p-Akt） and multidrng-resistance like protein （MRP） in normal pancreas tissues, chronic pancreatitis tissues and pancreatic carcinoma tissues was de- tected. The effects of LY294002 combined with gemcitabine on proliferation of PANC-1 cells and pro- tein levels of p-Akt and MRP were detected. The results showed that the positive expression rate of PI3K, p-Akt and MRP in pancreatic carcinoma tissues was significantly higher than that in normal pan- creas tissues and chronic pancreatitis tissues （P〈0.01 and P〈0.05 respectively）. LY294002 could effec- tively enhance the inhibitory effect of gemcitabine on proliferation of PANC-1 cells. Furthermore, Western blotting revealed that LY294002 combined with gemcitabine reduced the protein levels of p-Akt and MRP, which contributed to the inhibition of proliferation. It is concluded that LY294002 in combination with gemcitabine may represent an alternative therapy for pancreatic carcinoma.