scholarly journals HIF-1α RNAi Combined with Asparagus Polysaccharide Exerts an Antiangiogenesis Effect on Hepatocellular Carcinoma In Vitro and In Vivo

2021 ◽  
Vol 2021 ◽  
pp. 1-13
Author(s):  
Tingting Zhu ◽  
Ziwei Cheng ◽  
Xiaolin Peng ◽  
Dongwei Xing ◽  
Minguang Zhang
Keyword(s):  
Hepatocellular Carcinoma ◽  
Signaling Pathways ◽  
Primary Liver Cancer ◽  
Combined Treatment ◽  
Mapk Signaling ◽  
Comprehensive Treatment ◽  
Mapk Signaling Pathways ◽  
Hcc Cells

Background. Hepatocellular carcinoma (HCC) is the main form of primary liver cancer and is one of the most prevalent and life-threatening malignancies globally. Hypoxia activates hypoxia-inducible factor-1α (HIF-1α), which is the key factor in promoting angiogenesis in HCC. Currently, there are few studies on the effects of HIF-1α-targeted gene therapy combined with traditional Chinese herbal extracts. Objective. We investigated the effects of HIF-1α RNA interference (RNAi) combined with asparagus polysaccharide (ASP) on HCC in vitro and in vivo. Methods. CCK-8, wound-healing, transwell, and human umbilical vein endothelial cell tube formation assays were performed to evaluate the proliferation, migration, invasion, and angiogenesis of HCC cells in vitro. In addition, western blotting, qPCR, and immunohistochemistry were performed to detect the expression of HIF-1α, vascular endothelial growth factor, AKT, p-AKT, ERK, p-ERK, and CD34 in HCC cells. Results. The combination of HIF-1α RNAi and ASP significantly inhibited the proliferation, migration, invasion, and angiogenesis of SK-Hep1 and Hep-3B cells compared with the use of HIF-1α RNAi or ASP alone. In addition, this combined treatment was shown to exert these effects by regulating the PI3K and MAPK signaling pathways. These results were observed both in vitro and in vivo. Conclusion. Our study indicates that HIF-1α RNAi combined with ASP inhibits angiogenesis in HCC via the PI3K and MAPK signaling pathways. Thus, we suggest that this combination may be an effective method for the comprehensive treatment of HCC, which may provide new ideas for the treatment of other malignant tumors.

scholarly journals Inhibition effects of patchouli alcohol against influenza a virus through targeting cellular PI3K/Akt and ERK/MAPK signaling pathways

2019 ◽  
Vol 16 (1) ◽  
Author(s):  
Yunjia Yu ◽  
Yang Zhang ◽  
Shuyao Wang ◽  
Wei Liu ◽  
Cui Hao ◽  
...  
Keyword(s):  
Signaling Pathways ◽  
Influenza A ◽  
Plaque Assay ◽  
Mapk Signaling ◽  
Western Blot Assay ◽  
Patchouli Alcohol ◽  
Erk Mapk ◽  
Mapk Signaling Pathways

Abstract Background Patchouli alcohol (PA) is a tricyclic sesquiterpene extracted from Pogostemonis Herba, which is a traditional Chinese medicine used for therapy of inflammatory diseases. Recent studies have shown that PA has various pharmacological activities, including anti-bacterial and anti-viral effects. Methods In this study, the anti-influenza virus (IAV) activities and mechanisms were investigated both in vitro and in vivo. The inhibitory effects of PA against IAV in vitro were evaluated by plaque assay and immunofluorescence assay. The neuraminidase inhibition assay, hemagglutination inhibition (HI) assay, and western blot assay were used to explore the anti-viral mechanisms. The anti-IAV activities in vivo were determined by mice pneumonia model and HE staining. Results The results showed that PA significantly inhibited different IAV strains multiplication in vitro, and may block IAV infection through inactivating virus particles directly and interfering with some early stages after virus adsorption. Cellular PI3K/Akt and ERK/MAPK signaling pathways may be involved in the anti-IAV actions of PA. Intranasal administration of PA markedly improved mice survival and attenuated pneumonia symptoms in IAV infected mice, comparable to the effects of Oseltamivir. Conclusions Therefore, Patchouli alcohol has the potential to be developed into a novel anti-IAV agent in the future.

In vitro and in vivo efficacy and safety of tumor treating fields (TTFields) and sorafenib combination in hepatocellular carcinoma.

2020 ◽  
Vol 38 (4_suppl) ◽  
pp. 551-551
Author(s):  
Shiri Davidi ◽  
Catherine Tempel-Brami ◽  
Mijal Munster ◽  
Karnit Gotlib ◽  
Einav Zeevi ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Treatment Group ◽  
Combination Treatment ◽  
Combined Treatment ◽  
Efficacy And Safety ◽  
Tumor Treating Fields ◽  
Clonogenic Potential ◽  
Hcc Cells

551 Background: Hepatocellular carcinoma (HCC) is a leading global cause of cancer-related mortality. Sorafenib (oral multikinase inhibitor) is approved in patients with advanced HCC, yet survival benefit is limited. Tumor Treating Fields (TTFields) are an effective, anti-neoplastic treatment modality delivered via noninvasive, low intensity (1-3 V/cm), intermediate frequency (100-500 kHz), alternating electric fields. The study aim was to explore in vitro and in vivo effects of TTFields alone and combined with sorafenib for HCC treatment. Methods: HCC (HepG2 and Huh-7D12) cells were TTFields treated with at frequencies of 100-400 kHz for 72 hr using the inovitro system. Efficacy of TTFields and sorafenib combined treatment was tested at optimal frequency with various sorafenib concentrations. Cell counts, apoptosis induction, and clonogenic potential were determined. Healthy rats were used to assess safety of TTFields applied to the abdomen. N1S1 HCC cells were injected into the left hepatic lobe of Sprague Dawley rat; after 1 week, TTFields (1.2 V/cm) and sorafenib (10 mg/kg) were applied for 6 days. Tumor growth was evaluated using MRI. Results: The optimal TTFields frequency was 150 kHz in HepG2 and Huh-7D12 HCC cells. TTFields 150 kHz treatment (1.0 - 1.7 V/cm, 72 hr) led to cell count reductions (53-55%) and further decreases in clonogenic potential (65-69%). TTFields and sorafenib combination treatment led to a significant reduction in cell count (2-way ANOVA, P < 0.05) vs either treatment alone. Also, tumor growth was significantly reduced in the combined treatment group vs the control group (student t test, P < 0.01). Tumor volume (fold increase) in the combination treatment group (1.6) was significantly lower vs control (5.9, P < 0.0001), TTFields alone (3.3, P < 0.01), and sorafenib alone (2.3, P < 0.05) groups. Safety studies did not reveal any TTFields related adverse events with delivery to the rat abdomen. Conclusions: In vitro and in vivo data demonstrated efficacy and safety of TTFields in HCC; and improved efficacy in combination with sorafenib. A phase 2 study (HEPANOVA; NCT03606590) will explore the clinical potential of TTFields 150 kHz plus sorafenib.

scholarly journals Berbamine Exerts Anti-Inflammatory Effects via Inhibition of NF-κB and MAPK Signaling Pathways

2017 ◽  
Vol 41 (6) ◽  
pp. 2307-2318 ◽  
Author(s):  
Xiao-Jian Jia ◽  
Xi Li ◽  
Feng Wang ◽  
Han-Qing Liu ◽  
Da-Jun Zhang
Keyword(s):  
Signaling Pathways ◽  
Mapk Signaling ◽  
Inflammatory Factor ◽  
Anti Inflammatory ◽  
Underlying Mechanisms ◽  
Peritonitis Model ◽  
Mapk Signaling Pathways ◽  
Superoxide Release

Background/Aims: This study aimed to investigate the anti-inflammatory activity of Berbamine (BER), a bisbenzylisoquinoline alkaloid extracted from Berberis amurensis (Xiao Bo An), and the underlying mechanisms. Methods: Macrophages and neutrophils were treated with BER in vitro and stimulated with LPS and fMLP. The effects of BER on the expression of pro-inflammatory mediators in macrophages were evaluated with quantitative RT-PCR and ELISA. The effects of BER on the activation and superoxide release of neutrophils were determined with flow cytometry and WST-1 reduction test. The inhibitory effects of BER on the activation of signaling pathways related to inflammatory response in macrophages were evaluated by western blot analysis. In addition, a mouse peritonitis model was made by peritoneal injection of thioglycollate medium and anti-inflammatory effects of BER were investigated in vivo by quantitative analysis of pro-inflammatory factor production and leukocyte exudation. Results: BER significantly inhibited inflammatory factor expression by LPS-stimulated macrophages and suppressed activation and superoxide release of fMLP-stimulated neutrophils. In the mouse peritonitis model, BER significantly inhibited the activation of macrophages and exudation of neutrophils. According to analysis, BER significantly suppressed phosphorylation of NF-κB and MAPK (JNK and ERK1/2) signaling pathways in LPS-stimulated macrophages. Conclusions: Collectively, data from this study suggest that BER has anti-inflammatory potential, which is effected via inhibition of NF-κB and MAPK signaling pathways, and thus holds promise for treatment of inflammatory disease.

scholarly journals CircEpc1 Promotes Ricin Toxin-Induced Inflammation via Activation of NF-κB and MAPK Signaling Pathways by Sponging miR-5114

2021 ◽  
Vol 12 ◽  
Author(s):  
Mingxin Dong ◽  
Xiaohao Zhang ◽  
Haotian Yu ◽  
Yan Wang ◽  
Ying Chang ◽  
...  
Keyword(s):  
Signaling Pathways ◽  
Suppressive Effect ◽  
Mapk Signaling ◽  
Innate Immune ◽  
Circular Rnas ◽  
Inflammatory Injury ◽  
Ricin Toxin ◽  
Mapk Signaling Pathways

Increasing studies have concentrated on investigating circular RNAs (circRNAs) as pivotal regulators in the progression of numerous diseases and biological processes and abundant evidence shows that circRNAs are participated in the regulation of innate immune responses. Several studies showed that Ricin Toxin (RT) could induce inflammatory injury. There was no research on the particular functions and underlying mechanisms of circRNAs in RT-induced inflammation. In this study, RNA sequencing performed on RT-treated and normal RAW264.7 macrophage cells was used to investigated the differentially expressed circRNAs. Based on the dataset, the expression of circEpc1 (mmu_circ_0,000,842) was identified higher in RT-treated cells. Moreover, gain-and-loss function assays showed that circEpc1 function as a promoter in RT-induced inflammation in vivo and in vitro. Mechanistically, circEpc1 acted as a miR-5114 sponge to relieve the suppressive effect of miR-5114 on its target NOD2 and thereby activating NF-κB and MAPK signaling pathways. Our results illuminated a link between RT-induced inflammation and the circEpc1 regulatory loop and provided novel insight into the functions of circRNA in innate immune, which may emerge as a potential target in immunotherapy to control the RT-induced inflammatory injury.

scholarly journals CircEpc1 Promotes Ricin Toxin-Induced Inflammation Via Activation of NF-κB And MAPK Signaling Pathways By Sponging miR-5114

2021 ◽  
Author(s):  
Mingxin Dong ◽  
Xiaohao Zhang ◽  
Haotian Yu ◽  
Yan Wang ◽  
Ying Chang ◽  
...  
Keyword(s):  
Signaling Pathways ◽  
Suppressive Effect ◽  
Mapk Signaling ◽  
Innate Immune ◽  
Circular Rnas ◽  
Inflammatory Injury ◽  
Ricin Toxin ◽  
Mapk Signaling Pathways

Abstract Background: Increasing studies have concentrated on investigating circular RNAs (circRNAs) as pivotal regulators in the progression of numerous diseases and biological processes and abundant evidence shows that circRNAs are participated in the regulation of innate immune responses. Several studies showed that Ricin Toxin (RT) could induce inflammatory injury. There was no research on the particular functions and underlying mechanisms of circRNAs in RT-induced inflammation. Results: In this study, RNA sequencing performed on RT-treated and normal RAW264.7 macrophage cells was used to investigated the differentially expressed circRNAs. Based on the dataset, the expression of circEpc1 (mmu_circ_0000842) was identified higher in RT-treated cells. Moreover, gain-and-loss function assays showed that circEpc1 function as a promoter in RT-induced inflammation in vivo and in vitro. Mechanistically, circEpc1 acted as a miR-5114 sponge to relieve the suppressive effect of miR-5114 on its target NOD2 and thereby activating NF-κB and MAPK signaling pathways. Conclusions: Our results illuminated a link between RT-induced inflammation and the circEpc1 regulatory loop and provided novel insight into the functions of circRNA in innate immune, which may emerge as a potential target in immunotherapy to control the RT-induced inflammatory injury.

In vitro and in vivo anti-inflammatory effects of different extracts from Epigynum auritum through down-regulation of NF-κB and MAPK signaling pathways

2020 ◽  
Vol 261 ◽  
pp. 113105
Author(s):  
Meilian Yang ◽  
Yudan Wang ◽  
Gopal Patel ◽  
Qingwang Xue ◽  
Guy Sedar Singor Njateng ◽  
...  
Keyword(s):  
Signaling Pathways ◽  
Mapk Signaling ◽  
Down Regulation ◽  
Anti Inflammatory ◽  
Mapk Signaling Pathways

scholarly journals Cabozantinib-based combination therapy for the treatment of hepatocellular carcinoma

Gut ◽  
2020 ◽  
pp. gutjnl-2020-320716
Author(s):  
Runze Shang ◽  
Xinhua Song ◽  
Pan Wang ◽  
Yi Zhou ◽  
Xinjun Lu ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Therapeutic Efficacy ◽  
Checkpoint Inhibitor ◽  
Primary Liver Cancer ◽  
Combined Treatment ◽  
Tumour Regression ◽  
Liver Tumours ◽  
Multikinase Inhibitor

ObjectiveHepatocellular carcinoma (HCC) is the most common type of primary liver cancer with limited treatment options. Cabozantinib, an orally bioavailable multikinase inhibitor is now approved by Food and Drug Administration (FDA) for HCC patients. We evaluated the therapeutic efficacy of cabozantinib, either alone or in combination, in vitro and in vivo.DesignHuman HCC cell lines and HCC mouse models were used to assess the therapeutic efficacy and targeted molecular pathways of cabozantinib, either alone or in combination with the pan-mTOR inhibitor MLN0128 or the checkpoint inhibitor anti-PD-L1 antibody.ResultsCabozantinib treatment led to stable disease in c-Met/β-catenin and Akt/c-Met mouse HCC while possessing limited efficacy on Akt/Ras and c-Myc liver tumours. Importantly, cabozantinib effectively inhibited c-MET and ERK activity, leading to decreased PKM2 and increased p21 expression in HCC cells and in c-Met/β-catenin and Akt/c-Met HCC. However, cabozantinib was ineffective in inhibiting the Akt/mTOR cascade. Intriguingly, a strong inhibition of angiogenesis by cabozantinib occurred regardless of the oncogenic drivers. However, cabozantinib had limited impact on other tumour microenvironment parameters, including tumour infiltrating T cells, and did not induce programmed death-ligand 1 (PD-L1) expression. Combining cabozantinib with MLN0128 led to tumour regression in c-Met/β-catenin mice. In contrast, combined treatment with cabozantinib and the checkpoint inhibitor anti-PD-L1 antibody did not provide any additional therapeutic benefit in the four mouse HCC models tested.Conclusionc-MET/ERK/p21/PKM2 cascade and VEGFR2-induced angiogenesis are the primary targets of cabozantinib in HCC treatment. Combination therapies with cabozantinib and mTOR inhibitors may be effective against human HCC.

scholarly journals Evaluation of anticancer effects of Juniperus communis extract on hepatocellular carcinoma cells in vitro and in vivo

2021 ◽  
Author(s):  
Nan-Chieh Huang ◽  
Ru-Lai Huang ◽  
Xiao-Fan Huang ◽  
Kai-Fu Chang ◽  
Chien-Ju Lee ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Cell Cycle ◽  
Primary Liver Cancer ◽  
Scientific Evidence ◽  
Autocrine Signaling ◽  
Juniperus Communis ◽  
Anticancer Properties ◽  
Hcc Cells

Hepatocellular carcinoma (HCC) is the most common type of primary liver cancer and accounts for the fourth leading cause of all cancer deaths. Scientific evidence has found that plant extracts seem to be a reliable choice due to their multitarget effects against HCC. Juniperus communis has been used for centuries in traditional medicine and has reported its anticancer properties. As a result, the purpose of the study was to investigate the anticancer effect and mechanism of JCo extract on HCC in vitro and in vivo. In this study, we found that J. communis extract (JCo extract) inhibited the growth of human HCC cells by inducing cell cycle arrest at the G0/G1 phase, extensive apoptosis and suppressing metastatic protein expressions in HCC cells. Moreover, the combinational treatment of JCo and VP-16 was found to enhance the anti-cancer effect, revealing that JCo extract might have the potential to be utilized as an adjuvant to promote HCC treatment. Furthermore, in vivo study, JCo extract significantly suppressed HCC tumor growth and extended the lifespan with no or low systemic and pathological toxicity. JCo extract significantly upregulated the expression of pro-apoptotic proteins and tumor suppressor p53, suppressed VEGF/VEGFR autocrine signaling, downregulated cell cycle regulatory proteins and MMP2/MMP9 proteins. Overall, our results provide a basis for exploiting JCo extract as a potential anticancer agent against hepatocellular carcinoma.

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