T cell--associated immunoregulation and antiviral effect of oxymatrine in hydrodynamic injection HBV mouse model

Sang, Xiuxiu; Han, Yanzhong; Zhang, Cong'en; Shen, Hao; Yang, Zhao; Xiong, Yin; Liu, Huimin; Liu, Shijing; Li, Ruisheng; Yang, Ruihua; Wang, Jiabo; Wang, Xuejun; Bai, Zhaofang; Xiao, Xiaohe

doi:10.1016/j.apsb.2017.02.005

Cited by 31 publications

(15 citation statements)

References 37 publications

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“…The intracellular expression of cytokines in T-cells was analyzed using an eBioscience intracellular staining kit as previous reported 28 . Briefly, spleen cells from mice were incubated with PMA (100 ng/mL)/ionomycin (1 μg/mL) and monesine (1 μg/mL) in complete media at 37 °C for 6 h. The cells were first surface stained with CD4-FITC or CD8-APC for 15 min at 4 °C, then fixed and permeabilized with fixation and permeabilization wash buffers respectively.…”

Section: Methodsmentioning

confidence: 99%

SHP2 inhibition triggers anti-tumor immunity and synergizes with PD-1 blockade

Zhao

Guo

et al. 2019

Acta Pharmaceutica Sinica B

152

124

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Tyrosine phosphatase SHP2 is a promising drug target in cancer immunotherapy due to its bidirectional role in both tumor growth promotion and T-cell inactivation. Its allosteric inhibitor SHP099 is known to inhibit cancer cell growth both in vitro and in vivo . However, whether SHP099-mediated SHP2 inhibition retards tumor growth in vivo via anti-tumor immunity remains elusive. To address this, a CT-26 colon cancer xenograft model was established in mice since this cell line is insensitive to SHP099. Consequently, SHP099 minimally affected CT-26 tumor growth in immuno-deficient nude mice, but significantly decreased the tumor burden in CT-26 tumor-bearing mice with intact immune system. SHP099 augmented anti-tumor immunity, as shown by the elevated proportion of CD8 + IFN- γ + T cells and the upregulation of cytotoxic T-cell related genes including Granzyme B andPerforin , which decreased the tumor load. In addition, tumor growth in mice with SHP2-deficient T-cells was markedly slowed down because of enhanced anti-tumor responses. Finally, the combination of SHP099 and anti-PD-1 antibody showed a higher therapeutic efficacy than either monotherapy in controlling tumor growth in two colon cancer xenograft models, indicating that these agents complement each other. Our study suggests that SHP2 inhibitor SHP099 is a promising candidate drug for cancer immunotherapy.

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Section: Methodsmentioning

confidence: 99%

SHP2 inhibition triggers anti-tumor immunity and synergizes with PD-1 blockade

Zhao

Guo

et al. 2019

Acta Pharmaceutica Sinica B

152

124

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“…Especially, extensive researches have reported that OMT have anticancer effects by inducing cell cycle arrest, apoptosis and inhibition of angiogenesis in various cancer cells in vitro and in vivo (24). In the previous studies, immunoregulatory effects of OMT on hepatitis B of mice, rheumatoid arthritis in rats and mastitis in mice have been confirmed (25–27). Considering the extensive effects of OMT, we investigate the effect of OMT in combination with DDP on anti-tumor immunity in NSCLC and elucidate the potential mechanism.…”

Section: Introductionmentioning

confidence: 78%

Oxymatrine and Cisplatin Synergistically Enhance Anti-tumor Immunity of CD8+ T Cells in Non-small Cell Lung Cancer

Jin

Zou

et al. 2018

Front. Oncol.

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Oxymatrine (OMT) has shown broad antitumor activities for the treatment of several types of cancers. However, little is known about its effect on anti-tumor immunity. Combination therapy is a potentially promising strategy of cancer to enhance anticancer activity, overcome drug resistance, and lower treatment failure rate. In the present study, we demonstrated that the combination of OMT with cisplatin (DDP) synergistically inhibited non-small cell lung cancer (NSCLC) cells growth when co-cultured with peripheral blood mononuclear cells in vitro. Furthermore, the combination of OMT with DDP significantly inhibited the growth of Lewis lung cancer (LLC) mouse xenograft tumors. Flow cytometry analysis revealed that OMT and DDP synergistically increase the CD8+/ regulatory T cells ratio and enhanced more CD8+ T cells secreted cytokines of IFN-γ, TNF-α, and IL-2 in vivo. Mechanistically, upregulation of miR-155 and downregulation of suppressor of cytokine signaling-1 (SOCS1) were confirmed as a target signaling pathway to positively regulate the anti-tumor response of CD8+ T cells. Overall, OMT in combination with DDP showed outstanding synergistic anti-tumor immunity, suggesting that this beneficial combination may offer a potential immunotherapy for NSCLC patients.

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“…Our results also showed that in HBV-replicating mouse model, LWWL treatment significantly increased the frequency of CD3 + CD4 + T cells and serum IFN-γ production. IFN-γ is mainly generated by activated CD3 + CD4 + T cells, and IFN-γ has been proved to be able to inhibit HBV replication through triggering intracellular antiviral pathways ( Chokshi et al, 2014 ; Sang et al, 2017 ; Iannacone and Guidotti, 2021 ). We speculated that LWWL might play an anti-HBV role by enhancements of both IFN-β-mediated innate anti-HBV effect and IFN-γ-mediated acquired anti-HBV effect, whereas further studies are needed for the confirmation and elucidation of the context of the pathways.…”

Section: Discussionmentioning

confidence: 99%

Chinese Patent Medicine Liuweiwuling Tablet had Potent Inhibitory Effects on Both Wild-Type and Entecavir-Resistant Hepatitis B Virus (HBV) in vitro and Effectively Suppressed HBV Replication in Mouse Model

Liu

Yang

et al. 2021

Front. Pharmacol.

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Liuweiwuling Tablet (LWWL) is a licensed Chinese patent medicine (approval number: Z20060238) included in the national health insurance for anti-inflammation of chronic HBV infection, whereas its anti-HBV effect remains clarification. The study aimed to clarify its antiviral effect and related mechanisms. HepG2.2.15 cells (wild-type HBV-replicating cells) and HepG2. A64 cells (entecavir-resistant HBV-replicating cells) were used for in vitro test. Hydrodynamic injection-mediated HBV-replicating mouse model was used for in vivo test. Active compounds and related mechanisms for antiviral effect of LWWL were analyzed using network pharmacology and transcriptomics. The inhibition rates of LWWL (0.8 mg/ml) on HBV DNA, HBsAg, and pgRNA were 57.06, 38.55, and 62.49% in HepG2.2.15 cells, and 51.57, 17.57, and 53.88% in HepG2. A64 cells, respectively. LWWL (2 g kg−1 d−1 for 4 weeks)-treated mice had 1.16 log10 IU/mL decrease of serum HBV DNA, and more than 50% decrease of serum HBsAg/HBeAg and hepatic HBsAg/HBcAg. Compared to tenofovir control, LWWL was less effective in suppressing HBV DNA but more effective in suppressing HBV antigens. Thirteen differentially-expressed genes were found in relation to HBV-host interaction and some of them were enriched in interferon (IFN)-β pathway in LWWL-treated HepG2.2.15 cells. CD3+CD4+ T-cell frequency and serum IFN-γ were significantly increased in LWWL-treated mice compared to LWWL-untreated mice. Among 26 compounds with potential anti-HBV effects that were predicted by network pharmacology, four compounds (quercetin, luteolin, wogonin, and kaempferol) were experimentally confirmed to have antiviral potency. In conclusion, LWWL had potent inhibitory effect on both wild-type and entecavir-resistant HBV, which might be associated with increasing IFN-β and IFN-γ production.

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T cell--associated immunoregulation and antiviral effect of oxymatrine in hydrodynamic injection HBV mouse model

Cited by 31 publications

References 37 publications

SHP2 inhibition triggers anti-tumor immunity and synergizes with PD-1 blockade

SHP2 inhibition triggers anti-tumor immunity and synergizes with PD-1 blockade

Oxymatrine and Cisplatin Synergistically Enhance Anti-tumor Immunity of CD8+ T Cells in Non-small Cell Lung Cancer

Chinese Patent Medicine Liuweiwuling Tablet had Potent Inhibitory Effects on Both Wild-Type and Entecavir-Resistant Hepatitis B Virus (HBV) in vitro and Effectively Suppressed HBV Replication in Mouse Model

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