We are analyzing https://link.springer.com/article/10.1007/s00210-024-03530-9.

Title:
Carvacrol potentiates immunity and sorafenib anti-cancer efficacy by targeting HIF-1α/STAT3/ FGL1 pathway: in silico and in vivo study | Naunyn-Schmiedeberg's Archives of Pharmacology
Description:
Hypoxia and tumor cell immunological escape greatly hinder the hepatocellular carcinoma (HCC) treatment efficiency. This study is designed to investigate the capability of carvacrol (CVR) to enhance sorafenib (SOR) anti-cancer efficacy and modulate anti-HCC immunity. CVR target and biological activities were predicted using Swiss Target Prediction website and PASS web server. UALCAN and LinkedOmics databases were used to examine hypoxia-inducible factor 1-alpha (HIF-1α) expression and the relationship between studied genes and tumor clinical features. Kaplan–Meier plotter (KM plotter) and TISIDB databases were used to illustrate correlation of HIF-1α with HCC prognosis and immune infiltration. The binding affinities of CVR to p300, KAT2B, CREBBP, and Hsp90 were demonstrated by molecular docking. In vivo analysis was performed in male Sprague–Dawley rats. The STAT3, JAK2, and fibrinogen-like protein 1 (FGL1) expressions were assessed by qRT-PCR. FGL1 was determined by ELISA. CD8+ T cell number was counted by flow cytometry. HIF-1α was determined by immunohistochemistry. CVR showed an HIF-1α inhibitory potential, which is highly expressed in HCC tissues. Also, elevated HIF-1α expression has been found to be correlated with clinicopathological characteristics, poor survival in HCC patients, and tumor immune cell infiltration. CVR/SOR enhanced liver functions and decreased AFP level. CVR/SOR hindered HCC progression by downregulating STAT3, JAK2, and FGL1. CVR/SOR induced tumor immunity via increasing CD8+ T cells. CVR/SOR is a powerful combination for tumor repression and enhancing SOR efficiency in HCC by modulating FGL1. Moreover, CVR/SOR might exert the aforementioned effects through HIF-1α/STAT3/FGL1 pathway.
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28 years and 1 months (reg. 1997-05-29).

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Keywords {🔍}

hcc, hifα, pubmed, cvr, article, google, scholar, expression, cas, group, hepatocellular, carcinoma, sor, cells, cancer, protein, tumor, fgl, carvacrol, liver, wang, fig, central, cell, survival, cvrsor, gene, immune, rats, sorafenib, study, hypoxiainducible, hsp, stat, significant, compared, analysis, immunity, activity, cmc, zhang, hypoxia, factor, level, liu, binding, patients, significance, full, chen,

Topics {✒️}

inhibiting hif-1α/ppar-γ/pkm2-mediated glycolysis hif-1α/ppar-γ/pkm2 axis modulating hif-1α/jak2/stat3/fgl1 pathway absence-ii versus alpha-fetoprotein targeting hypoxia-inducible factor-1α erk1/2-hif-1α-p300/creb axis myeloid-derived suppressor cells targeting hif-1α/p300 complex hypoxia-inducible factor-2α overexpression hypoxia-inducible factor-1 alpha hypoxia-inducible factor-1α sorafenib-resistant hepatoma cells hypoxia-mediated sorafenib resistance voltage-gated ion channels hif-1α/stat3/fgl1 pathway hypoxia-inducible factors 1α asymptomatic hiv-1-infected subjects hypoxia enhanced mdsc-mediated il-8–nf-κb axis hif-1/pd-l1 axis albendazole-loaded cubosomes interrupt vhl-dependent hif-1α high hif-1α expression elevated hif-1α expression hindering hif-1α activity enzyme-linked immunosorbent assay cvr/sor anti-hcc activity sars-cov-2 main protease newly synthesized hif-1α abo el-magd nf abo el-magd conceptualized lymphocyte-induced antitumor immunity preferably large-scale validation hypoxia increases pd-l1 hif-1α nuclear translocation upregulating pd-l1 expression il-1β-induced elevation modulate anti-hcc immunity oxygen-dependent degradation pathway hepatic hif-1α level hif-1α expression based encourage hepatocyte growth hif-1α protein expression sorafenib-resistant tumor treatment low hif-1α expression hypoxia-inducible factors inhibiting il-6/stat3 pathway article download pdf improves liver functions abo el-magd revised

Schema {🗺️}

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      headline:Carvacrol potentiates immunity and sorafenib anti-cancer efficacy by targeting HIF-1α/STAT3/ FGL1 pathway: in silico and in vivo study
      description:Hypoxia and tumor cell immunological escape greatly hinder the hepatocellular carcinoma (HCC) treatment efficiency. This study is designed to investigate the capability of carvacrol (CVR) to enhance sorafenib (SOR) anti-cancer efficacy and modulate anti-HCC immunity. CVR target and biological activities were predicted using Swiss Target Prediction website and PASS web server. UALCAN and LinkedOmics databases were used to examine hypoxia-inducible factor 1-alpha (HIF-1α) expression and the relationship between studied genes and tumor clinical features. Kaplan–Meier plotter (KM plotter) and TISIDB databases were used to illustrate correlation of HIF-1α with HCC prognosis and immune infiltration. The binding affinities of CVR to p300, KAT2B, CREBBP, and Hsp90 were demonstrated by molecular docking. In vivo analysis was performed in male Sprague–Dawley rats. The STAT3, JAK2, and fibrinogen-like protein 1 (FGL1) expressions were assessed by qRT-PCR. FGL1 was determined by ELISA. CD8+ T cell number was counted by flow cytometry. HIF-1α was determined by immunohistochemistry. CVR showed an HIF-1α inhibitory potential, which is highly expressed in HCC tissues. Also, elevated HIF-1α expression has been found to be correlated with clinicopathological characteristics, poor survival in HCC patients, and tumor immune cell infiltration. CVR/SOR enhanced liver functions and decreased AFP level. CVR/SOR hindered HCC progression by downregulating STAT3, JAK2, and FGL1. CVR/SOR induced tumor immunity via increasing CD8+ T cells. CVR/SOR is a powerful combination for tumor repression and enhancing SOR efficiency in HCC by modulating FGL1. Moreover, CVR/SOR might exert the aforementioned effects through HIF-1α/STAT3/FGL1 pathway.
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         Liver cancer
         Tumor immunity
         Drug resistance
         Hypoxia
         Hepassocin
         Tumor microenvironment
         Pharmacology/Toxicology
         Neurosciences
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               type:PostalAddress
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               type:PostalAddress
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      name:Department of Pharmacology and Biochemistry, Faculty of Pharmacy, Horus University-Egypt, New Damietta, Egypt
      name:Biochemistry Department, Faculty of Pharmacy, Mansoura University, Mansoura, Egypt
      name:Biochemistry Department, Faculty of Pharmacy, Mansoura University, Mansoura, Egypt

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