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    Online Resource
    Online Resource
    Ginsenoside Rb1 Lessens Gastric Precancerous Lesions by Interfering With β-Catenin/TCF4 Interaction
    Frontiers Media SA ; 2021
    In:  Frontiers in Pharmacology Vol. 12 ( 2021-9-14)
    Details
    In: Frontiers in Pharmacology, Frontiers Media SA, Vol. 12 ( 2021-9-14)
    Abstract: Background: Seeking novel and effective therapies for gastric precancerous lesions (GPL) is crucial to reducing the incidence of gastric cancer. Ginsenoside Rb1 (GRb1) is a major ginsenoside in ginseng and has been proved to possess multiple bioactivities. However, whether GRb1 could protect against GPL and the underlying mechanisms have not been explored. Methods: We evaluated the effects of GRb1 on gastric precancerous lesions in rats on macroscopic, microscopic and ultramicroscopic levels. Then, an antibody array was employed to screen differential expression proteins (DEPs). Validation for the targeting DEP and investigation for the possible mechanism was conducted using immunohistochemistry, qRT-PCR, TUNEL apoptosis assay, immunoprecipitation and immunoblotting. Results: GRb1 was found to reverse intestinal metaplasia and a portion of dysplasia in the MNNG-induced GPL rats. The antibody array assay revealed seven DEPs in GPL rats as compared to control rats (5 DEPs were up-regulated, while two DEPs were down-regulated). Among the DEPs, β-catenin, beta-NGF and FSTL1 were significantly down-regulated after GRb1 administration. Our validation results revealed that enhanced protein expression and nuclear translocation of β-catenin were present in animal GPL samples. In addition, analysis of human gastric specimens demonstrated that β-catenin up-regulation and nuclear translocation were significantly associated with advanced GPL pathology. GRb1 intervention not only decreased protein expression and nuclear translocation of β-catenin, but interfered with β-catenin/TCF4 interaction. Along with this, declined transcriptional and protein expression levels of downstream target genes including c-myc, cyclin D1 and Birc5 were observed in GRb1-treated GPL rats. Conclusion: GRb1 is capable of preventing the occurrence and progression of GPL, which might be contributed by diminishing protein expression and nuclear translocation of β-catenin and interfering with β-catenin/TCF4 interaction.
    Type of Medium: Online Resource
    ISSN: 1663-9812
    URL: Article
    DOI: 10.3389/fphar.2021.682713
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2021
    detail.hit.zdb_id: 2587355-6
    SSG: 15,3
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  • 2
    Online Resource
    Online Resource
    Atractylenolide III Attenuates Angiogenesis in Gastric Precancerous Lesions Through the Downregulation of Delta-Like Ligand 4
    Frontiers Media SA ; 2022
    In:  Frontiers in Pharmacology Vol. 13 ( 2022-6-30)
    Details
    In: Frontiers in Pharmacology, Frontiers Media SA, Vol. 13 ( 2022-6-30)
    Abstract: Background: Blocking and even reversing gastric precancerous lesions (GPL) is a key measure to lower the incidence of gastric cancer. Atractylenolide III (AT-III) is a mainly active component of the Atractylodes rhizome and has been widely used in tumor treatment. However, the effects of AT-III on GPL and its mechanisms have not been reported. Methods: H & amp; E staining and AB-PAS staining were employed to evaluate the histopathology in the gastric mucosa. In parallel, CD34 immunostaining was performed for angiogenesis assessment, and transmission electron microscope for microvessel ultrastructural observation. Investigation for the possible mechanism in vivo and in vitro was conducted using immunohistochemistry, RT-qPCR and western blotting. Results: In most GPL specimens, AT-III treatment reduced microvascular abnormalities and attenuated early angiogenesis, with the regression of most intestinal metaplasia and partial dysplasia. Meanwhile, the expression of VEGF-A and HIF-1α was enhanced in GPL samples of model rats, and their expressions were decreased in AT-III-treated GPL rats. Moreover, DLL4 mRNA and protein expression were higher in GPL rats than in control rats. DLL4 protein expression was significantly enhanced in human GPL tissues. In addition, AT-III treatment could diminish DLL4 mRNA level and protein expression in the MNNG-induced GPL rats. In vitro study showed that in AGS and HGC-27 cells, DLL4 mRNA level and protein expression were significantly decreased after AT-III treatment. However, AT-III had no significant regulatory effect on Notch1 and Notch4. Conclusion: AT-III treatment is beneficial in lessening gastric precancerous lesions and attenuating angiogenesis in rats, and that may be contributed by the decrease of angiogenesis-associated HIF-1α and VEGF-A, and downregulation of DLL4.
    Type of Medium: Online Resource
    ISSN: 1663-9812
    URL: Article
    DOI: 10.3389/fphar.2022.797805
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2022
    detail.hit.zdb_id: 2587355-6
    SSG: 15,3
    Location Call Number Limitation Availability
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  • 3
    Online Resource
    Online Resource
    Natural compounds targeting glycolysis as promising therapeutics for gastric cancer: A review
    Frontiers Media SA ; 2022
    In:  Frontiers in Pharmacology Vol. 13 ( 2022-11-10)
    Details
    In: Frontiers in Pharmacology, Frontiers Media SA, Vol. 13 ( 2022-11-10)
    Abstract: Gastric cancer, a common malignant disease, seriously endangers human health and life. The high mortality rate due to gastric cancer can be attributed to a lack of effective therapeutic drugs. Cancer cells utilize the glycolytic pathway to produce energy even under aerobic conditions, commonly referred to as the Warburg effect, which is a characteristic of gastric cancer. The identification of new targets based on the glycolytic pathway for the treatment of gastric cancer is a viable option, and accumulating evidence has shown that phytochemicals have extensive anti-glycolytic properties. We reviewed the effects and mechanisms of action of phytochemicals on aerobic glycolysis in gastric cancer cells. Phytochemicals can effectively inhibit aerobic glycolysis in gastric cancer cells, suppress cell proliferation and migration, and promote apoptosis, via the PI3K/Akt, c-Myc, p53, and other signaling pathways. These pathways affect the expressions of HIF-1α, HK2, LDH, and other glycolysis-related proteins. This review further assesses the potential of using plant-derived compounds for the treatment of gastric cancer and sheds insight into the development of new drugs.
    Type of Medium: Online Resource
    ISSN: 1663-9812
    URL: Article
    DOI: 10.3389/fphar.2022.1004383
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2022
    detail.hit.zdb_id: 2587355-6
    SSG: 15,3
    Location Call Number Limitation Availability
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    Online Resource
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