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- W2358049806 abstract "Antitumor activity and the mechanism of CPUY013, a novel Topo I inhibitor, on gastric adenocarcinoma BGC823 cells were studied in vitro and in vivo. The proliferation was investigated by MTT assay and colony formation assay. Apoptosis was determined by both dual fluorescence staining with AO and EB and DNA agarose gel electrophoresis analysis methods. Nude mice model of BGC823 xenograft tumor was established by subcutaneous inoculation. The suppression activity of the CPUY013 by intragastric administration on xenograft mice model was detected. The change of cell cycle was studied by flow cytometry assay. The expressions of Topo I, widetype p53, active caspase-3, bcl-2 and bax proteins were analyzed by Western blotting assay. Results showed that CPUY013 could inhibit BGC823 cell proliferation at a certain range of dose. The flow cytometry analysis showed that CPUY013 and topoecan (TPT) led to a decrease in the proportion of G1 phase cells and an increase in the proportion of S phase cells, suggesting that they arrested the transition of tumor cells from S phase to G2 phase. The sub-G1 group was analyzed by flow cytometry. Compared with control, after 48 h treatment with CPUY013 or TPT, the sub-G1 group significantly increased in a dose-dependent manner. CPUY013 and TPT induced apoptosis in tumor cells. Cells treated with CPUY013 for 48 h were stained with AO/EB mixture. Then the cells were observed under fluorescence microscope. And it was found that early and late apoptosis cells were identified by perinuclear condensation of chromatin stained by AO/EB, respectively. Necrotic cells were identified by uniform labeling with EB. With the increase of concentration of CPUY013 and TPT, these morphological changes under the fluorescence microscope become clearer, indicating that the proportion of apoptosis cells increased gradually. By using JC-1 kit, loss of deltapsim was also detected in BGC823 cells treated with CPUY013 and TPT, which represent mitochondria function. And characteristic DNA ladder was observed apparently in BGC823 cells treated with CPUY013. When the xenograft tumor mice were treated with 150 mg x kg(-1) CPUY013, the tumor growth inhibition rate was 62.1%. The expression of bax and p53 proteins increased significantly and bcl-2 and bcl-2/bax decreased after the treatment of the CPUY013. The CPUY013 down-regulated Topo I protein expression and up-regulated active caspase-3 protein expression. The novel Topo I inhibitor CPUY013 can significantly suppress the growth of BGC823 xenograft tumor in vivo and inhibit the proliferation by inducing apoptosis of BGC823 cells in vitro." @default.
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- W2358049806 date "2008-08-01" @default.
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- W2358049806 title "[Effects of CPUY013, a novel Topo I inhibitor, on human gastric adenocarcinoma BGC823 cells in vitro and in vivo]." @default.
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