Objective To analyze the expression level of ATP5A1 in gastric carcinoma and its influence on the prognosis of the patients and glucose metabolism in the tumor cells.Methods We retrospectively analyzed the data of 115 patients undergoing radical resection of gastric carcinoma in our hospital from February,2013 to November,2016.ATP5A1 expression in the surgical specimens were detected using immunohistochemistry,and the long-term prognosis of the patients with high(n=58)and low ATP5A1 expression(n=57)were analyzed.In gastric carcinoma MGC803 cells,the effects of lentivirus-mediated ATP5A1 knockdown or overexpression on glucose metabolism were investigated.We also observed the growth and glucose metabolism of xenografts derived from MGC803 cells with ATP5A1 knockdown or overexpression in nude mice.Results ATP5A1 was significantly overexpressed in gastric carcinoma tissues in close correlation with blood CEA and CA19-9 levels,pathological grade,T stage and N stage(P<0.05).ATP5A1 overexpression was an independent risk factor for a significantly lowered 5-year survival rate of patients with gastric carcinoma(P<0.05).ROC curve analysis demonstrated the predictive value of high ATP5A1 expression for the patients'prognosis(P<0.001).In MGC803 cells,ATP5A1 overexpression significantly up-regulated cellular glucose uptake and lactate production and increased the protein levels of HK2,PFK1,and LDHA(P<0.05),while ATP5A1 knockdown produced the opposite changes(P<0.05).In the tumor-bearing mice,overexpression of ATP5A1 increased glucose metabolism of the tumor cells and promoted tumor growth(P<0.05).Overexpression of ATP5A1 promoted the expressions of p-JNK and p-JUN in MGC803 cells(P<0.05),and the JNK inhibitor SP600125 significantly inhibited the enhancement of cellular glucose metabolism induced by ATP5A1 overexpression(P<0.05).Conclusion High ATP5A1 expression in gastric cancer is associated a poor long-term prognosis of the patients,and its effect is mediated at least partly by promoting glucose metabolism of the cells through the JNK/JUN pathway.

Objective To analyze the expression level of ATP5A1 in gastric carcinoma and its influence on the prognosis of the patients and glucose metabolism in the tumor cells.Methods We retrospectively analyzed the data of 115 patients undergoing radical resection of gastric carcinoma in our hospital from February,2013 to November,2016.ATP5A1 expression in the surgical specimens were detected using immunohistochemistry,and the long-term prognosis of the patients with high(n=58)and low ATP5A1 expression(n=57)were analyzed.In gastric carcinoma MGC803 cells,the effects of lentivirus-mediated ATP5A1 knockdown or overexpression on glucose metabolism were investigated.We also observed the growth and glucose metabolism of xenografts derived from MGC803 cells with ATP5A1 knockdown or overexpression in nude mice.Results ATP5A1 was significantly overexpressed in gastric carcinoma tissues in close correlation with blood CEA and CA19-9 levels,pathological grade,T stage and N stage(P<0.05).ATP5A1 overexpression was an independent risk factor for a significantly lowered 5-year survival rate of patients with gastric carcinoma(P<0.05).ROC curve analysis demonstrated the predictive value of high ATP5A1 expression for the patients'prognosis(P<0.001).In MGC803 cells,ATP5A1 overexpression significantly up-regulated cellular glucose uptake and lactate production and increased the protein levels of HK2,PFK1,and LDHA(P<0.05),while ATP5A1 knockdown produced the opposite changes(P<0.05).In the tumor-bearing mice,overexpression of ATP5A1 increased glucose metabolism of the tumor cells and promoted tumor growth(P<0.05).Overexpression of ATP5A1 promoted the expressions of p-JNK and p-JUN in MGC803 cells(P<0.05),and the JNK inhibitor SP600125 significantly inhibited the enhancement of cellular glucose metabolism induced by ATP5A1 overexpression(P<0.05).Conclusion High ATP5A1 expression in gastric cancer is associated a poor long-term prognosis of the patients,and its effect is mediated at least partly by promoting glucose metabolism of the cells through the JNK/JUN pathway.

Objective To investigate the effects of kuwanon G(KG)on proliferation,apoptosis,migration and invasion of gastric cancer cells and the molecular mechanisms.Methods The effects of KG on proliferation and growth of gastric cancer cells were assessed with CCK-8 assay and cell clone formation assay,by observing tumor formation on the back of nude mice and using immunohistochemical analysis of Ki-67.The effect of KG on cell apoptosis was analyzed using Annexin V-FITC/PI apoptosis detection kit,Western blotting and TUNEL staining.The effects of KG on cell migration and invasion were detected using Transwell migration and invasion assay and Western blotting for matrix metalloproteinase(MMP).The role of phosphatidylinositol 3-kinase(PI3K)/protein kinase B(AKT)/mammalian target of rapamycin(mTOR)pathway in KG-mediated regulation of gastric cancer cell proliferation,migration,and invasion was verified by Western blotting and rescue assay.Results KG significantly inhibited proliferation and reduced clone formation ability of gastric cancer cells in a concentration-dependent manner(P<0.05).KG treatment also increased apoptosis,enhanced the expressions of cleaved caspase-3 and Bax,down-regulated Bcl-2,lowered migration and invasion capacities and inhibited the expression of MMP2 and MMP9 in gastric cancer cells(P<0.05).Mechanistic validation showed that KG inhibited the activation of the PI3K/AKT/mTOR pathway,and IGF-1,an activator of the PI3K/AKT/mTOR pathway,reversed the effects of KG on proliferation,migration and invasion of gastric cancer cells(P<0.05).Conclusion KG inhibits proliferation,migration and invasion and promotes apoptosis of gastric cancer cells at least in part by inhibiting the activation of the PI3K/AKT/mTOR pathway.

Objective To investigate the effects of kuwanon G(KG)on proliferation,apoptosis,migration and invasion of gastric cancer cells and the molecular mechanisms.Methods The effects of KG on proliferation and growth of gastric cancer cells were assessed with CCK-8 assay and cell clone formation assay,by observing tumor formation on the back of nude mice and using immunohistochemical analysis of Ki-67.The effect of KG on cell apoptosis was analyzed using Annexin V-FITC/PI apoptosis detection kit,Western blotting and TUNEL staining.The effects of KG on cell migration and invasion were detected using Transwell migration and invasion assay and Western blotting for matrix metalloproteinase(MMP).The role of phosphatidylinositol 3-kinase(PI3K)/protein kinase B(AKT)/mammalian target of rapamycin(mTOR)pathway in KG-mediated regulation of gastric cancer cell proliferation,migration,and invasion was verified by Western blotting and rescue assay.Results KG significantly inhibited proliferation and reduced clone formation ability of gastric cancer cells in a concentration-dependent manner(P<0.05).KG treatment also increased apoptosis,enhanced the expressions of cleaved caspase-3 and Bax,down-regulated Bcl-2,lowered migration and invasion capacities and inhibited the expression of MMP2 and MMP9 in gastric cancer cells(P<0.05).Mechanistic validation showed that KG inhibited the activation of the PI3K/AKT/mTOR pathway,and IGF-1,an activator of the PI3K/AKT/mTOR pathway,reversed the effects of KG on proliferation,migration and invasion of gastric cancer cells(P<0.05).Conclusion KG inhibits proliferation,migration and invasion and promotes apoptosis of gastric cancer cells at least in part by inhibiting the activation of the PI3K/AKT/mTOR pathway.