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The modification of Wnt and Notch signaling pathways by hypoxia, and its association with osteoblast proliferation and apoptosis remain to be fully elucidated. To investigate Wnt-Notch crosstalk, and its role in hypoxia-induced osteoblast proliferation and apoptosis regulation, the present study investigated the effects of cobalt-mimicked hypoxia on the mouse pre-osteoblast-like cell line, MC3T3-E1, when the Notch signals were repressed using a γ-secretase inhibitor DAPT. The data showed that the cobalt-mimicked hypoxia suppressed cell proliferation under normal conditions, but increased cell proliferation under conditions of Notch repression, in a concentration-dependent manner. The results of western blot and reverse transcription-quantitative polymerase chain reaction analyses showed that the cobalt treatment increased the levels of activated β-catenin protein and the expression levels of the target genes, axis inhibition protein 2 and myelocytomatosis oncogene, under DAPT-induced Notch repression. However, no significant changes were found in the expression levels of the Notch intracellular domain protein or the Notch target gene, hes1. In a β-catenin gene-knockdown experiment, the proliferation of the MC3T3-E1 cells under hypoxia were decreased by DAPT treatment, and knockdown of the expression of hypoxia-inducible factor-1α (HIF-1α) suppressed the cobalt-induced increase in Wnt target gene levels. No significant difference in cell proliferation rate was found following DAPT treatment when the expression of HIF-1α was knocked down. The results of the present study showed the opposing effects of Wnt and Notch signaling under cobalt-mimicked hypoxia, which were partially regulated by HIF-1α, The results also showed that osteoblast proliferation was dependent on Wnt-Notch signal crosstalk. [ABSTRACT FROM AUTHOR]

The present study aimed to determine the antitumor effects of polysaccharides extracted from Pleurotus ostreatus mycelium on gastric cancer in vitro and in vivo. Polysaccharides were extracted from Pleurotus ostreatus mycelium and an antitumor component, known as Pleurotus ostreatus mycelium polysaccharides 2 (POMP2), with a relative molecular weight of 29 kDa, was then sequentially purified using Sephadex G200 size-exclusion chromatography and diethylaminoethyl-52 cellulose ion-exchange chromatography. The MTT method was used to determine the proliferation of BGC-823 cells treated with POMP2; cell migration assay, colony formation assay and in vivo antitumor tests were used to assess the effect of POMP2 on migration, cell survival and the in vivo tumor formation of BGH-823 cells. Results of the MTT assay indicated that POMP2 had a marked inhibitory effect on the BGC-823 human gastric cancer cell line; when administered at a concentration of 400 mg/l for 72 h, the rate of inhibition was 35.6%. In addition, the colony forming capacity of the BGC-823 cells was significantly reduced following treatment with POMP2. A migration assay indicated that the invasive capabilities of the BGC-823 cells were also significantly inhibited by POMP2. Furthermore, in vivo tests of mice engrafted with BGC-823 cancer cells demonstrated that both tumor weight and volume were markedly reduced following two weeks of treatment with POMP2. The results of the present study suggested that the polysaccharide POMP2 may have a potential application as a natural antitumor treatment for gastric cancer. [ABSTRACT FROM AUTHOR]