【摘 要】
：
The present study was designed to determine the potential of a bisphosphonate(BP)derivative [2-(6-amino-purine-9-yl)-1-hydroxy-phosphine acyl ethyl] phospho
【机 构】
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DepartmentofSurgery,theSecondAffiliatedHospitalofHebeiMedicalUniversity,Shijiazhuang050017,Hebei,Chi
【出 处】
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2015全国中医药生物化学与分子生物学年会
论文部分内容阅读
The present study was designed to determine the potential of a bisphosphonate(BP)derivative [2-(6-amino-purine-9-yl)-1-hydroxy-phosphine acyl ethyl] phosphonic acid(CP)as a novel therapeutic agent in human gastric cancer.Effects of CP on the induction of apoptosis and underlying mechanisms were investigated in human gastric cancer cell lines.Moreover,tumor growth inhibition by CP was assessed in a xenograft tumor mouse model.CP induced the activation of caspase-9 in the gastric cancer cell line SGC-7901,as evidenced by the cleavage of endogenous substrate poly(ADP-ribose)polymerase(PARP).CP treatment also increased expression of pro-apoptotic proteins Bax and Bad,with a concomitant decrease in the anti-apoptotic protein Bcl-2.Furthermore,activation of extracellular signal-regulated kinase(ERK)was induced by CP,and the ERK-specific inhibitor PD98059 and ERK small interfering RNA(siRNA)could antagonize the CP-mediated apoptosis.Additionally,in nude xenografted mice,CP significantly inhibited the tumor growth of SGC-7901 cells.In conclusion,CP induced apoptosis in gastric cancer cells through activation of the ERK signaling pathway.Moreover,CP treatment caused a significant inhibition of tumor growth in vivo.Therefore,CP may be developed as a candidate drug for use in prevention and treatment of gastric cancer.
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