This study examined the combined effects of oxaliplatin and LY294002, a phosphatidylinositol 3'-kinase inhibitor, on gastric cancer. In vitro, combination treatment resulted in enhanced inhibition of cell growth and increased apoptosis compared to oxaliplatin alone. In vivo, combination treatment inhibited tumor growth more than oxaliplatin alone by activating the death receptor pathway. The enhanced anti-cancer effect of combination treatment was associated with inhibition of Akt and NF-κB activation and increased expression of proteins involved in death receptor mediated apoptosis.

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LY294002 potentiates the anti-most cancers result of oxaliplatin for gastric most cancers by
using death receptor pathway
Jie Liu, Xue-Qiong Fu, Wei Zhou, Hong-Gang Yu, Jie-Ping Yu, He-Sheng Luo
Jie Liu, Xue-Qiong Fu, Wei Zhou, Institute of Gastroenterology and Hepatology, Wuhan
University Health-related University, Wuhan 430060, Hubei Province, China Hong-Gang Yu,
Jie-Ping Yu, He-Sheng Luo, Section of Gastroenterology, Renmin Medical center of Wuhan
College, Wuhan 430060, Hubei Province, China Writer contributions: Liu J, Zhou W and Fu
XQ executed the vast majority of experiments Yu HG offered very important reagents and
analytical tools and was also included in modifying the manuscript Luo HS and Yu JP
developed the research and supplied economic support for this work Liu J wrote the
manuscript. Supported by The National Pure Science Foundation of China, No. 30470782
Correspondence to: He-Sheng Luo, Professor, Section of Gastroenterology, Renmin Medical
center of Wuhan University, 238 Jiefang Road, Wuhan 430060, Hubei Province, China.
luotangwh@gmail.com Telephone: +86-27-88042134 Fax: +86-27-88042292 Acquired:
September 14, 2010 Revised: December 14, 2010 Acknowledged: December 21, 2010
Posted on the internet: January 14, 2011
tion and cell apoptosis in vitro , and elevated tumor expansion inhibition and cell demise in
the tumor mass in vivo . In MKN45 and AGS cells, oxaliplatin remedy promoted equally
protein kinase B (Akt) and NFB activation, although pretreatment with LY294002
substantially attenuated oxaliplatin-induced Akt activity and NFB binding. LY294002
promoted oxaliplatin-induced Fas ligand (FasL) manifestation, Fas-connected passing away
domain protein recruitment, caspase-8, Bid, and caspase-3 activation, and the brief form of
cellular caspase-eight/FLICEinhibitory protein (c-FLIPS) inhibition. In vivo , LY294002
inhibited oxaliplatin-induced activation of Akt and NFB, and improved oxaliplatin-induced
reflection of FasL, inhibition of c-FLIPS, and activation of caspase-8, Bid, and caspase-three.
Summary: Mix of oxaliplatin and LY294002 was therapeutically promising for gastric cancer
cure. The enhanced sensitivity of the put together treatment was related with the activation of
the loss of life receptor pathway.
?2011 Baishideng. All legal rights reserved.
Summary
Aim: To look at the effects of blended treatment of oxaliplatin and phosphatidylinositol 3'-
kinase inhibitor, 2-(four-morpholinyl)-8-phenyl-4H-1-benzopyran-four-a single (LY294002) for
gastric most cancers. Approaches: Mobile viability was evaluated by three-(4,5-
dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. Apoptotic cells had been
detected by circulation cytometric assessment and terminal deoxynucleotidyl transferase-

2. mediated dUTP nick conclude labeling assay. Western blotting and immuno-precipitation
have been used to look at protein expression and recruitment, respectively. Nuclear
component B (NFB) binding routines have been investigated working with electrophoretic
mobility change assay. Nude mice ended up applied to investigate tumor progress. Benefits:
Remedy with mixed oxaliplatin and LY294002 resulted in enhanced cell growth inhibi-
Essential phrases: Gastric most cancers Oxaliplatin Phosphatidylinositol 3'-kinase/Akt
pathway Loss of life receptor pathway Apoptosis LY294002 Peer reviewers: Jun-Hyeog
Jang, Professor, Chief, Section
of Biochemistry, Inha University University of Medication, JungGu, Incheon four hundred-
712, South Korea Very long-Bin Jeng, MD, Organ Transplantation Middle, China Health care
University Hospital, two Yuh-Der Road, Taichung 40447, Taiwan, China Tatsuo Kanda, MD,
PhD, Division of Digestive and Basic Operation, Graduate School of Clinical and Dental
Sciences, Niigata University, Niigata Metropolis 951-8510, Japan Liu J, Fu XQ, Zhou W, Yu
HG, Yu JP, Luo HS. Protease Suitable for Newbies, Protease For the Amateurs, Protease
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