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Phosphoinositide 3-kinase/Akt pathway plays an important role in chemoresistance of gastric cancer cells against etoposide and doxorubicin induced cell death.

Phosphoinositide 3-kinase/Akt pathway plays an important role in chemoresistance of gastric cancer cells against etoposide and doxorubicin induced cell death. Research Abstract Details 

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  • Phosphoinositide 3-kinase/Akt pathway plays an important role in chemoresistance of gastric cancer cells against etoposide and doxorubicin induced cell death. Abstract Text:

    hong-gang yuHong-Gang Yu,yao-wei aiYao-Wei Ai,liang-liang yuLiang-Liang Yu,xiao-dong zhouXiao-Dong Zhou,jin liuJin Liu,jun-hua liJun-Hua Li,xi-ming xuXi-Ming Xu,song liuSong Liu,jing chenJing Chen,fen liuFen Liu,yuan-ling qiYuan-Ling Qi,quanjun dengQuanjun Deng,jun caoJun Cao,shi-quan liuShi-Quan Liu,he-sheng luoHe-Sheng Luo,jie-ping yuJie-Ping Yu,hong-gang yuHong-Gang Yu,yao-wei aiYao-Wei Ai,liang-liang yuLiang-Liang Yu,xiao-dong zhouXiao-Dong Zhou,jin liuJin Liu,jun-hua liJun-Hua Li,xi-ming xuXi-Ming Xu,song liuSong Liu,jing chenJing Chen,fen liuFen Liu,yuan-ling qiYuan-Ling Qi,quanjun dengQuanjun Deng,jun caoJun Cao,shi-quan liuShi-Quan Liu,he-sheng luoHe-Sheng Luo,jie-ping yuJie-Ping Yu,

    The major obstacle to successful treatment of gastric cancer is chemotherapy resistance. Our study was designed to investigate the role of phosphoinositide 3-kinase (PI3K)/Akt pathway in the development of chemoresistance in gastric cancer. In the present study, elevated Akt expression and Akt phosphorylation (Ser 473), as well as decreased PTEN expression were observed in 28 cases of gastric cancer tissues. Etoposide and doxorubicin stimulated Akt and PI3K activities in 2 gastric cancer cell lines (BGC-823 and SGC-7901), and the activities were concentration and time-dependent. Up-regulation of PTEN expression in BGC-823 cells by PEAK8-PTEN transient transfection obviously decreased the basal and anticancer drugs induced Akt activities, then sensitized BGC-823 cells to etoposide and doxorubicin. Pretreatment of BGC-823 and SGC-7901 cells with wortmannin, a PI3K inhibitor, attenuated cells's resistance to etoposide and doxorubicin. In addition, pretreatment of wortmannin blocked etoposide and doxorubicin induced IkappaB-alpha degradation, NFkappaB activation, phosphorylation of Akt, MDM-2 and forkhead transcription factors. Wortmannin pretreatment also promoted the accumulation of p27/Kip, but inhibited the Mcl-1 expression. Furthermore, wortmannin promoted etoposide and doxorubicin induced caspase-3, caspase-9 activation and poly ADP-ribose polymerase cleavage. Taken together, the observations indicate the PI3K/Akt pathway plays an important role in the chemoresistance of gastric cancer cells. A new strategy for combined chemotherapy of gastric cancer should be designed to more specifically block PI3K/Akt pathway and then decrease the amount of resistant cells.

    Phosphoinositide 3-kinase/Akt pathway plays an important role in chemoresistance of gastric cancer cells against etoposide and doxorubicin induced cell death. Publishing Authors By Initials

    hg yuHG Yu,yw aiYW Ai,ll yuLL Yu,xd zhouXD Zhou,j liuJ Liu,jh liJH Li,xm xuXM Xu,s liuS Liu,j chenJ Chen,f liuF Liu,yl qiYL Qi,q dengQ Deng,j caoJ Cao,sq liuSQ Liu,hs luoHS Luo,jp yuJP Yu,hg yuHG Yu,yw aiYW Ai,ll yuLL Yu,xd zhouXD Zhou,j liuJ Liu,jh liJH Li,xm xuXM Xu,s liuS Liu,j chenJ Chen,f liuF Liu,yl qiYL Qi,q dengQ Deng,j caoJ Cao,sq liuSQ Liu,hs luoHS Luo,jp yuJP Yu,

    For similar abstracts research abstracts see: abstracts research

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    Phosphoinositide 3-kinase/Akt pathway plays an important role in chemoresistance of gastric cancer cells against etoposide and doxorubicin induced cell death. Journal Published:

    PUBLICATION TYPE: Research Support, Non-U.S. Gov

    Journal: International journal of cancer. Journal internati

    VOLUME: 122

    Page Numbers: 433-43

    Journal Abbreviation: Int. J. Cancer

    ISSN: 1097-0215

    DAY: 15

    MONTH: Jan

    YEAR: 2008

    Phosphoinositide 3-kinase/Akt pathway plays an important role in chemoresistance of gastric cancer cells against etoposide and doxorubicin induced cell death. Information

    Number of References:

    LANGUAGE: eng

    NlmUniqueID: 42124

    Phosphoinositide 3-kinase/Akt pathway plays an important role in chemoresistance of gastric cancer cells against etoposide and doxorubicin induced cell death. Keywords Mesh Terms:

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    Grant and Affiliation Information for Phosphoinositide 3-kinase/Akt pathway plays an important role in chemoresistance of gastric cancer cells against etoposide and doxorubicin induced cell death.

    AFFILIATION: Department of Gastroenterology, Renmin Hospital of Wuhan Univeristy, Wuhan, China. yuhonggang@yahoo.com

    Country: United States

    United States Research PublicationUnited States Research Publication

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    MEDLINETA: Int J Cancer

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