Gehua Jiecheng Decoction Inhibits Diethylnitrosamine-Induced Hepatocellular Carcinoma in Mice by Improving Tumor Immunosuppression Microenvironment

Cheng, Changpei; Shou, Qiyang; Lang, Jiali; Jin, Lu; Liu, Xia; Tang, Dongdong; Yang, Zhu; Fu, Huiying

doi:10.3389/fphar.2020.00809

Cited by 15 publications

(5 citation statements)

References 52 publications

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“…Furthermore, it has developed a mouse model (DEN/CCL4) with a high tumor HCC incidence and low death rate that may be used in a short time (8 weeks). For the long duration of 44 weeks of the DENinduced HCC model, a huge number of cancer nodules on the surface of the liver and ROS generation were observed (Cheng et al, 2020).…”

Section: Discussionmentioning

confidence: 99%

“…An inflammatory microenvironment generated by prolonged inflammatory cells and factors may also transform into an immunosuppressive microenvironment, thereby promoting angiogenesis and tumor progression. Immunotherapy is a novel and efficient tumor therapy (Cheng et al, 2020). Also, developing new therapeutics that target cell cycle and apoptosis dysregulation, inflammation, and fibrogenesis is crucial (Galicia-Moreno et al, 2021).…”

Section: Introductionmentioning

confidence: 99%

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Adipose mesenchymal stem cell-based therapy: Anticancer molecular mechanisms in hepatoma model and bone marrow

Atia

Sallam²,

aly³

et al. 2022

International Journal of Cancer and Biomedical Research

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Background: Adipose-derived mesenchymal stem cells (AD-MSCs) can be used as therapeutic agents for the treatment of patients with HCC Aim: The study aimed to establish an animal model for hepatocellular carcinoma (HCC) by using diethyl nitrosamine (DEN) and carbon tetrachloride (CCl4) in a short time. Materials and Methods: Forty-five female rats were subdivided into three groups: control (G1), HCC model (G2), and therapeutic (G3). Each rat in the G2 groups was injected with DEN and after 1 week was injected again with CCl4, whereas G3 rats were injected with AD-MSCs immediately after the tumor appeared. Results: The injection of DEN/CCl4 was correlated with the increase in alanine transaminase, aspartate aminotransferase, and alpha-fetoprotein levels. Also, it caused oxidative stress as indicated by an increase in nuclear factor-erythroid factor 2-related factor-2 (Nrf2), vascular endothelial growth factor levels, and fibrosis. However, BCL2-associated X protein (BAX) was decreased. Transplantation of AD-MSCs induced apoptosis by increasing BAX and decreasing Nrf2 levels, which significantly inhibited angiogenesis. Histologically, our results indicated that AD-MSCs alleviated hepatocellular carcinoma, fibrosis, and nuclear morphology. Additionally, the bone marrow (BM) maturation index ratio parameter was restored to a normal stage. Conclusion: AD-MSCs have a wide range of targeted anticarcinogenic properties and can regenerate BM precursors of cellularity.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Adipose mesenchymal stem cell-based therapy: Anticancer molecular mechanisms in hepatoma model and bone marrow

Atia

Sallam²,

aly³

et al. 2022

International Journal of Cancer and Biomedical Research

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“…The famous Chinese medicine Gehua Jiecheng Decoction can inhibit the expression of CCL-2 in the liver while effectively inhibiting the development of tumor cells and reducing the tumor area. In addition, the expression of inflammatory factors and angiogenesis factors in the tumor is also reduced to varying degrees to antagonize the immunosuppressive effect of the liver cancer microenvironment ( 121 ). There is also evidence that blocking CCL-2 can promote TME recovery from inhibition ( 122 ).…”

Section: The Value Of Tls For Phc Treatmentmentioning

confidence: 99%

Tertiary Lymphatic Structures in Primary Hepatic Carcinoma: Controversy Cannot Overshadow Hope

et al. 2022

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Tertiary lymphoid structures (TLSs) are organized aggregates of immune cells found in the tumor microenvironment. TLS can influence primary hepatic carcinoma (PHC) occurrence and have an active role in cancer. TLS can promote or inhibit the growth of PHC depending on their location, and although available findings are controversial, they suggest that TLS have a protective role in PHC tissues and a non-protective role in paracancerous tissues. In addition, the cellular composition of TLS can also influence the outcome of PHC. As an immunity marker, TLS can act as a marker of immunotherapy to predict its effect and help to identify patients who will respond well to immunotherapy. Modulation of TLS formation through the use of chemokines/cytokines, immunotherapy, or induction of high endothelial vein to interfere with tumor growth has been studied extensively in PHC and other cancers. In addition, new tools such as genetic interventions, cellular crosstalk, preoperative radiotherapy, and advances in materials science have been shown to influence the prognosis of malignant tumors by modulating TLS production. These can also be used to develop PHC treatment.

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“…Initially, our research group focused on studying the sobering and liver-protective effects of Gehua jiecheng fang and found that these plants also possess anticancer properties. Among them, PF is the primary component, and there is literature supporting its use in HCC care (Cheng et al, 2020). The effect of Gehua jiecheng fang on excessive drinking is detailed in PiWeiLun (Chen et al, 2023).…”

Section: Introductionmentioning

confidence: 99%

Puerariae Flos promotes apoptosis through the ESR1-ERK1/2 signaling pathway to intervene in alcoholic hepatocellular carcinoma

Li,

An,

Cheng

et al. 2024

Preprint

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Ethnopharmacological relevance: Increasing evidence indicates that conventional traditional Chinese medicine (TCM) plays a cardinal role in oncological remedies. Initially, our research group focused on research related to the sobering-up and liver-protecting effects of Gehua jiecheng fang, and found that these plants also have anticancer properties. Among these pathogens, Puerariae Flos (PF) is the main component of the fungus, and there is also literature supporting the use of PF for HCC care. Aim of the study: PF is utilized to treat tumors in China. However, its effect on and mechanism involved in alcohol-associated hepatocellular carcinoma (alcohol-related HCC) remain elusive. This investigation aimed to address this knowledge gap through experiments and bioinformatics. Materials and methods: Limid chromatography-tandem mass spectrometry (LC‒MS/MS) was used as an initial method for identifying chemical compounds that were present in the drug sera. The prognostic DEGs were determined using univariate Cox regression analysis. The diagnostic value of the DEGs was estimated by constructing survival curves and utilizing the curved TCGA and GEO datasets, which are connected to alcoholic HCC according to their recipient operation characteristics (ROC). The affinity and stability between the target and predictive chemical compounds were checked by means of molecular docking and molecular dynamics simulations. Furthermore, the selected genes were subjected to clinical correlation analysis and KEGG analysis. The impact of PF on migration and cell proliferation was evaluated via western blotting. Results: LC‒MS/MS revealed 68 components and identified 844 objects, 63 of which overlapped with the aims of patients with alcoholic HCC. Seven methods were used to determine that the ESR1 and CDK1 genes have advantages in the diagnosis of alcoholic HCC. Molecular docking and molecular dynamics demonstrated strong binding affinities between key components andESR1. Pathway analysis revealed that the two core genes were involved in apoptosis in a complex manner, with ESR1 showing enrichment in the chemogenic receptor activation pathway. The diagnostic significance of ESR1 was confirmed by Western blot and in vitro experiments. Conclusion: PF inhibits the migration and proliferation of alcohol-related HCC cells by regulating the ESR1/ERK1/2 pathway to promote cell apoptosis.

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Gehua Jiecheng Decoction Inhibits Diethylnitrosamine-Induced Hepatocellular Carcinoma in Mice by Improving Tumor Immunosuppression Microenvironment

Cited by 15 publications

References 52 publications

Adipose mesenchymal stem cell-based therapy: Anticancer molecular mechanisms in hepatoma model and bone marrow

Adipose mesenchymal stem cell-based therapy: Anticancer molecular mechanisms in hepatoma model and bone marrow

Tertiary Lymphatic Structures in Primary Hepatic Carcinoma: Controversy Cannot Overshadow Hope

Puerariae Flos promotes apoptosis through the ESR1-ERK1/2 signaling pathway to intervene in alcoholic hepatocellular carcinoma

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