Chrysin inhibits hepatocellular carcinoma progression through suppressing programmed death ligand 1 expression

Rong, Weihao; Wan, Nanyan; Zheng, Xiao; Shi, Gaofeng; Jiang, Cuihua; Pan, Ke; Gao, Meng; Yin, Zhiqi; Gao, ZeJun; Zhang, Jian

doi:10.1016/j.phymed.2021.153867

Cited by 26 publications

(11 citation statements)

References 49 publications

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“…In our study, proportions of G0G1 and G2M phases in the h-SIRT6 group were obviously higher than in the control and h-NULL groups, whereas the proportion of S phase in the h-SIRT6 group was obviously lower. These results indicated SIRT6 over expression could increase G0G1 and G2M phases arrest, reduce the proportion of the (33,34). Our results showed SIRT6 over expression inhibited the AKT1/ mTOR pathway, promoted apoptosis and cell cycle arrest, down-regulated the expression of PD-L1, and reduced its migration and proliferation abilities.…”

Section: Discussionmentioning

confidence: 53%

“…Studies have shown the downregulation of PD-L1 expression can reshape the tumor immune microenvironment and enhance the T cell-mediated anti-tumor immune response and IL-2 level ( 33 , 34 ). Our results showed SIRT6 over expression inhibited the AKT1/mTOR pathway, promoted apoptosis and cell cycle arrest, down-regulated the expression of PD-L1, and reduced its migration and proliferation abilities.…”

Section: Discussionmentioning

confidence: 99%

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Inhibition of the AKT1/mTOR pathway through SIRT6 over expression downregulated the expression of programmed death-ligand 1 and prolonged overall survival in lung adenocarcinoma

Yuan¹,

Lin²,

Wu³

et al. 2023

Ann Transl Med

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Background Programmed death-ligand 1 (PD-L1) is a common biomarker of immune checkpoint inhibitors (ICIs). The purpose of our study was to investigate the relationship between Sirtuin 6 (SIRT6) and PD-L1 expressions in lung adenocarcinoma. Methods Recombinant plasmids containing green fluorescent protein (GFP)/no SIRT6 (h-NULL) and GFP/SIRT6 (h-SIRT6) were constructed and transfected into A549 cells by lentivirus as vector. The experiment was divided into control, h-NULL and h-SIRT6 groups. We detected apoptosis and the cell cycle by flow cytometry and observed migration and proliferation by wound-healing assays and methyl thiazolyl tetrazolium. The expressions of SIRT6, PD-L1, serine/threonine protein kinase-1 (AKT1), mammalian target of rapamycin (mTOR), B-cell lymphoma-2 (BCL-2) associated X protein (BAX), and BCL-2 were detected by real-time fluorescence quantitative reverse transcription polymerase chain reaction (qRT-PCR) and Western blot. We retrospectively analyzed the relationship between SIRT6 expression and survival in lung adenocarcinoma treated by ICIs. Results The expression of BAX, apoptosis rate, and proportion of G0G1 and G2M phases in the h-SIRT6 group were higher than in the control and h-NULL groups (P<0.05). The expressions of PD-L1, BCL-2, AKT1, and mTOR migration and proliferation rates and proportion of S phase in the h-SIRT6 group were lower than in the control and h-NULL groups (P<0.05). Survival in lung adenocarcinoma with high SIRT6 expression was better than with low SIRT6 expression. Conclusions SIRT6 over expression, through the inhibition of the AKT1/mTOR pathway, down-regulated PD-L1 expression, influenced biological behaviors, and prolonged survival of lung adenocarcinoma. SIRT6 expression may be a potential gene biomarker for immunotherapy in lung adenocarcinoma.

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Section: Discussionmentioning

confidence: 53%

Section: Discussionmentioning

confidence: 99%

Inhibition of the AKT1/mTOR pathway through SIRT6 over expression downregulated the expression of programmed death-ligand 1 and prolonged overall survival in lung adenocarcinoma

Yuan¹,

Lin²,

Wu³

et al. 2023

Ann Transl Med

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“…Mo et al found that icaritin interacts with IKK-α to interfere with the NF-κB pathway and inhibit the expression of PD-L1 in liver cancer cells [ 24 ]. Chrysin downregulates PD-L1 expression in HCC by blocking the STAT3 and NF-κB pathways in vitro and in vivo [ 25 ]. In addition, the CHIP-seq analysis in this study revealed that in HCC, NF-κB can bind to multiple sites in the promoter region of PD-L1 and participates in regulating the expression level of PD-L1.…”

Section: Discussionmentioning

confidence: 99%

Midazolam exhibits antitumour and enhances the efficiency of Anti-PD-1 immunotherapy in hepatocellular carcinoma

Kang

Zheng

et al. 2022

Cancer Cell Int

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Background Midazolam (MDZ) is an anaesthetic that is widely used for anxiolysis and sedation. More recently, MDZ has also been described to be related to the outcome of various types of carcinomas. However, how MDZ influences the progression of hepatocellular carcinoma (HCC) and its effects on the biological function and tumour immune microenvironment of this type of tumour remain unknown. Methods The effects of MDZ on the proliferation, invasion, and migration of HCC cell lines were examined in vitro using the Cell Counting Kit 8 (CCK8), 5-ethynyl-2ʹ-deoxyuridine (EdU), Transwell, and wound healing assays. Additionally, western blotting was employed to confirm that PD-L1 was expressed. Chromatin immunoprecipitation-seq (ChIP-seq) analysis was used to pinpoint the transcriptional regulation regions of NF-κB and programmed death-ligand 1 (PD-L1). A C57BL/6 mouse model was used to produce subcutaneous HCC tumors in order to evaluate the in vivo performance of MDZ. Mass spectrometry was also used to assess changes in the tumour immunological microenvironment following MDZ injection. Results The HCC-LM3 and Hep-3B cell lines’ proliferation, invasion, and migration were controlled by MDZ, according to the results of the CCK8, EdU, Transwell, and wound healing assays. PD-L1 expression was shown by ChIP-seq analysis to be boosted by NF-κB, and by Western blotting analysis, it was shown that MDZ downregulated the expression of NF-κB. Additionally, in vivo tests revealed that intraperitoneal MDZ injections reduced HCC tumor development and enhanced the effectiveness of anti-PD-1 therapy. The CD45+ immune cell proportions were higher in the MDZ group than in the PBS group, according to the mass spectrometry results. Injection of MDZ resulted in a decrease in the proportions of CD4+ T cells, CD8+ T cells, natural killer (NK) cells, monocytes, Tregs, and M2 macrophages and a rise in the proportion of dendritic cells. Additionally, the concentrations of the cytokines IFN-g and TNF-a were noticeably raised whereas the concentrations of the CD8+ T-cell fatigue markers ICOS, TIGIT, and TIM3 were noticeably lowered. Conclusion According to this study, MDZ inhibited the progression of HCC by inhibiting the NF-κB pathway and reducing the exhaustion of CD8+ T cells. In clinical practice, MDZ combined with anti-PD-1 therapy might contribute to synergistically improving the antitumor efficacy of HCC treatment.

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“…84 Chrysin, a bioactive flavonoid from propolis, honey, and blue passion flower, was found to effectively inhibit hepatocellular carcinoma progression through suppressing PD-L1 expression via blocking JAK/START3 and NF-B pathways and might have the potential to be an immune checkpoint inhibitor targeting PD-L1. 85 Kaempferol (KO) and its glycosyl compound kaempferol 7-O-rhamnoside (KR) were proved to be potent inhibitors on PD-1/PD-L1 blockade by directly targeting both PD-1 and PD-…”

Section: Natural Productsmentioning

confidence: 99%

Progress in small-molecule inhibitors targeting PD-L1

Xu,

Kong,

Zhu

et al. 2024

RSC Med. Chem.

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Chrysin inhibits hepatocellular carcinoma progression through suppressing programmed death ligand 1 expression

Cited by 26 publications

References 49 publications

Inhibition of the AKT1/mTOR pathway through SIRT6 over expression downregulated the expression of programmed death-ligand 1 and prolonged overall survival in lung adenocarcinoma

Inhibition of the AKT1/mTOR pathway through SIRT6 over expression downregulated the expression of programmed death-ligand 1 and prolonged overall survival in lung adenocarcinoma

Midazolam exhibits antitumour and enhances the efficiency of Anti-PD-1 immunotherapy in hepatocellular carcinoma

Progress in small-molecule inhibitors targeting PD-L1

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