Weipiling decoction alleviates N-methyl-N-nitro-N′-nitrosoguanidine-induced gastric precancerous lesions via NF-κB signalling pathway inhibition

Yang, Penghui; Yang, Hongmei; Zhou, Hengli; Li, Qiuyue; Wei, Sufen; Wang, Qi; Yan, Yan; Liu, Yongqiang; Pan, Huafeng; Li, Siyi

doi:10.1186/s13020-022-00663-y

Cited by 4 publications

(6 citation statements)

References 50 publications

(66 reference statements)

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“…On the other hand, glutamic pyruvic transaminase and glutamic oxaloacetic transaminase increased, and liver function was significantly affected. Third, it regulates NF-κB signaling pathway affects the development of inflammation 16,17 , when NF-κB rises, this signal pathway is obviously activated, which leads to more significant inflammatory reaction, promotes the edema, destruction and repeated proliferation of cells, and increases the probability of cells with malignant phenotype, thus further promoting the progress of tumors. Therefore, in the experimental results, we found that in the model group, NF-κB increased significantly with obvious inflammatory cell infiltration, but it not emerge in normal tissues [18][19][20][21] .…”

Section: Discussionmentioning

confidence: 99%

Effect of FXR agonist GW4064 in the treatment of hilar cholangiocarcinoma in rats

Wang

Zhang

Luo

et al. 2022

Sci Rep

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The study objective was to observe the treatment effect of the farnesoid X receptor (FXR) agonist GW4064 in a rat model of hilar cholangiocarcinoma to explore a new therapeutic target for gene therapy for hilar cholangiocarcinoma. Eighty male Wistar rats were randomly divided into four groups (treatment group, model group, control group and sham operation group, 20 rats in each group). The four groups were fed a standard diet. The treatment group and the model group were injected with a suspension of cholangiocarcinoma QBC939 cells into the hilar bile duct with a microsyringe, the control group was injected with normal saline, and the sham operation group was not injected with anything. A modified tail suspension test (TST) was used to evaluate the vitality of the rats. At 4 weeks, one rat in the treatment group and model group was euthanized, and the changes in the hilar bile duct were recorded. The procedure was repeated at 6 weeks. After 6 weeks, hilar cholangiocarcinoma occurred in the treatment group and model group. Then, the treatment group was injected with GW4064 intraperitoneally at a dose of 50 mg/kg/day. One week after injection, the rats in the four groups were euthanized. Pathological examination confirmed that tumours had formed, and hilar bile duct tissues were taken from the four groups. FXR, Bsep, Ntcp and NF-κB expression in the hilar bile duct was detected by real-time polymerase chain reaction (RT–PCR) and immunohistochemistry. After three weeks, the rats in the treatment group and model group ate less, and their weight was significantly reduced. Six weeks later, hilar cholangiocarcinoma was detected in the treatment group and model group. After treatment with GW4064, the ratios of FXR/GAPDH mRNA, Bsep/GAPDH mRNA, Ntcp/GAPDH mRNA and NF-κBp65/GAPDH mRNA were significantly different among the four groups. Under a light microscope, FXR protein reacted with anti-FXR antibody, Bsep protein reacted with anti-Bsep antibody, Ntcp protein reacted with anti-Ntcp antibody and NF-κBp65 protein reacted with anti-NF-κBp65 antibody, and they showed granular expression. Every pathological section included 4,800 cells, and there were different numbers of positive cells in each group. FXR expression in the hilar cholangiocarcinoma of rats was significantly lower than that in normal hilar bile duct tissues. GW4064 increased the expression of FXR in tumour tissues. These findings suggest that FXR may be a new therapeutic target and that GW4064 may be helpful in the treatment of hilar cholangiocarcinoma.

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Section: Discussionmentioning

confidence: 99%

Effect of FXR agonist GW4064 in the treatment of hilar cholangiocarcinoma in rats

Wang

Zhang

Luo

et al. 2022

Sci Rep

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“…MNNG can induce gastric cancer by regulating inflammation, cell damage, cell differentiation mitochondrial dysfunction, glycolysis pathogenesis and oxidative stress processes ( Cai et al, 2018 ; Zhao et al, 2019a ; Cai et al, 2019 ; Cui et al, 2021 ; Wen et al, 2021 ; Gunes-Bayir et al, 2022 ). MNNG promotes the occurrence and development of gastric cancer by regulating processes such as autophagy, EMT, apoptosis, proliferation, angiogenesis, gastric epithelial dysplasia, malignant transformation and change endogenous metabolites ( Zhao et al, 2019b ; Deng et al, 2019 ; Wu and Hui, 2020 ; Liang et al, 2022a ; Cai et al, 2022 ; Chen et al, 2022 ; Peng et al, 2022 ; Yang et al, 2022 ; Xie et al, 2023 ).Therefore, there is an urgent need to find an effective and low side effect intervention or treatment strategy. In recent years, phytochemicals and active ingredients of herbal medicine have showed excellent application prospects in the prevention and treatment of gastric cancer.…”

Section: Effects Of N-nitrosamines and Mnng On The Occurrence And Pro...mentioning

confidence: 99%

The effect of phytochemicals in N-methyl-N-nitro-N-nitroguanidine promoting the occurrence and development of gastric cancer

Chen

Zhang

et al. 2023

Front. Pharmacol.

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Gastric cancer is a common malignant tumor of the digestive tract, with a low early diagnosis rate. N-methyl-N-nitro-N-nitroguanidine (MNNG) is one of the main risk factors for gastric cancer. Phytochemicals are healthy active substances derived from vegetables, fruits, nuts, tea, herbal medicines and other plants. Taking phytochemicals is a very promising strategy for the prevention and treatment of gastric cancer. Many studies have proved that phytochemicals have protective effects on MNNG induced gastric cancer via inhibiting cell proliferation, enhancing immunity, suppressing cell invasion and migration, inducing apoptosis and autophagy, blocking angiogenesis, inhibiting Helicobacter pylori infection as well as regulating metabolism and microbiota. The intervention and therapeutic effects of phytochemicals in MNNG induced gastric cancer have attracted more and more attention. In order to better study and explore the role, advantages and challenges of phytochemicals in MNNG induced gastric cancer, we summarized the intervention and therapeutic effects of phytochemicals in MNNG induced gastric cancer. This review may help to further promote the research and clinical application of phytochemicals in MNNG induced gastric cancer, and provide some new insights.

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“…The transition from normal gastric mucosal cells to cancer cells does not occur suddenly, but through a stage called gastric precancerous lesions (GPL) 2 . GPL refers to pathological changes that are more likely to transform into cancer tissue but lacks a specific definition 3–8 . According to Correa's cascade, GPL mainly includes chronic atrophic gastritis (CAG), intestinal metaplasia (IM), and dysplasia (DYS) 2 .…”

Section: Introductionmentioning

confidence: 99%

“…2 GPL refers to pathological changes that are more likely to transform into cancer tissue but lacks a specific definition. [3][4][5][6][7][8] According to Correa's cascade, GPL mainly includes chronic atrophic gastritis (CAG), intestinal metaplasia (IM), and dysplasia (DYS). 2 It is worth noting that GPL has the characteristics of bidirectional transformation, and the malignant transformation of gastric mucosal epithelial cells can be effectively reversed through early intervention and treatment.…”

Section: Introductionmentioning

confidence: 99%

Effect of Helicobacter pylori eradication on gastric precancerous lesions: A systematic review and meta‐analysis

Zhu,

Zhang,

et al. 2023

Helicobacter

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BackgroundThe question of whether eradication of Helicobacter pylori (Hp) can reverse gastric precancerous lesions, including intestinal metaplasia, remains uncertain, leading to ongoing debate. Therefore, a meta‐analysis was performed to evaluate the effect of Hp eradication on gastric precancerous lesions.Materials and MethodsPubMed, Embase, Cochrane Library, Web of Science, Scopus database, and ClinicalTrials.gov were systematically searched from inception to April 2023 for studies that explored the impact of Hp eradication on gastric precancerous lesions. Risk ratios (RRs) and their 95% confidence intervals (95% CIs) were selected as the effect size. We used the random‐effects model to assess pooled data. We also performed quality assessments, subgroup analyses, and sensitivity analyses.ResultsFifteen studies were included. Compared with placebo, Hp eradication could significantly prevent the progression of gastric precancerous lesions (RR = 0.87, 95% CI: 0.81–0.94, p < 0.01) and reverse them (RR = 1.32, 95% CI: 1.17–1.50, p < 0.01). Then, specific precancerous lesions were further explored. The progression of intestinal metaplasia was significantly prevented by Hp eradication compared to placebo or no treatment (RR = 0.80, 95% CI: 0.69–0.94, p < 0.01). Moreover, compared with placebo or no treatment, Hp eradication also improved chronic atrophic gastritis (RR = 1.84, 95% CI: 1.30–2.61, p < 0.01) and intestinal metaplasia (RR = 1.41, 95% CI: 1.15–1.73, p < 0.01). However, in terms of preventing dysplasia progression (RR = 0.86, 95% CI: 0.37–2.00) and improving dysplasia (RR = 0.89, 95% CI: 0.47–1.70), Hp eradication had no advantage compared to placebo or no treatment.ConclusionsHp eradication therapy could prevent the progression of gastric precancerous lesions and reverse them. Notably, intestinal metaplasia can be reversed, but this may only be appropriate for patients with epigenetic alterations and milder lesions.

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Weipiling decoction alleviates N-methyl-N-nitro-N′-nitrosoguanidine-induced gastric precancerous lesions via NF-κB signalling pathway inhibition

Cited by 4 publications

References 50 publications

Effect of FXR agonist GW4064 in the treatment of hilar cholangiocarcinoma in rats

Effect of FXR agonist GW4064 in the treatment of hilar cholangiocarcinoma in rats

The effect of phytochemicals in N-methyl-N-nitro-N-nitroguanidine promoting the occurrence and development of gastric cancer

Effect of Helicobacter pylori eradication on gastric precancerous lesions: A systematic review and meta‐analysis

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