LY294002 enhances inhibitory effect of gemcitabine on proliferation of human pancreatic carcinoma PANC-1 cells.
10.1007/s11596-013-1071-5
- Author:
Xiao-yu KE
1
;
Yu WANG
;
Zuo-qi XIE
;
Zhi-qing LIU
;
Cui-fang ZHANG
;
Qiu ZHAO
;
Dong-liang YANG
Author Information
1. Department of Infectious Diseases, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China. jessicawarm@hotmail.com
- Publication Type:Journal Article
- MeSH:
Adult;
Antimetabolites, Antineoplastic;
administration & dosage;
Cell Proliferation;
drug effects;
Chromones;
administration & dosage;
Deoxycytidine;
administration & dosage;
analogs & derivatives;
Dose-Response Relationship, Drug;
Drug Synergism;
Drug Therapy, Combination;
methods;
Enzyme Inhibitors;
administration & dosage;
Female;
Humans;
Male;
Middle Aged;
Morpholines;
administration & dosage;
Pancreatic Neoplasms;
drug therapy;
pathology;
Phosphatidylinositol 3-Kinases;
antagonists & inhibitors;
Treatment Outcome;
Tumor Cells, Cultured
- From:
Journal of Huazhong University of Science and Technology (Medical Sciences)
2013;33(1):57-62
- CountryChina
- Language:English
-
Abstract:
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 applied as an inhibitor of PI3K, in combination with gemcitabine on proliferation of PANC-1 cells was investigated. The expression of PI3K, phosphorylated Akt (p-Akt) and multidrug-resistance like protein (MRP) in normal pancreas tissues, chronic pancreatitis tissues and pancreatic carcinoma tissues was detected. The effects of LY294002 combined with gemcitabine on proliferation of PANC-1 cells and protein 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 pancreas tissues and chronic pancreatitis tissues (P<0.01 and P<0.05 respectively). LY294002 could effectively 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.
