Abstract
The purpose of this study was to investigate the therapeutic effect of berberine (BBR) on MNNG-induced chronic atrophic gastritis (CAG) and the possible mechanism of BBR through TGF-β1/PI3K signal pathway. GES-1 were pretreated with MNNG for 2 h before BBR treatment in all procedures. Cell viability was quantified by cell counting kit-8, and GES-1 morphology and proliferation were detected by high content screening (HCS) assay. The rat model of CAG was established by MNNG, and the therapeutic effect of BBR on stomach histopathology and serum supernatant were analyzed in vivo. In addition, the possible mechanism of BBR was further discussed, and the expression of related genes and proteins in TGF-β1/PI3K signal pathway was detected. The results showed that BBR could significantly improve the survival rate and morphological changes of GES-1, improve the gastric tissue injury of CAG rats, and reduce the expression of G-17 and inflammatory factors IL-8, TNF-α, IL-6 and IL-1β. In addition, BBR down-regulated the expression of TGF-β1 axis-related signals such as TGF-β1, PI3K, p-Akt/Akt, p-mTOR/mTOR and P70S6K, and promoted the expression of PTEN, LC3-II and Beclin-1. In Conclusion, BBR can improve CAG which may be closely related to TGF-β1/PI3K signal pathway.
Highlights
Gastric cancer (GC) is the second leading cause of cancer-related death worldwide (Hallowell et al, 2019; Liou et al, 2020)
The results showed that 40 μM MNNG had the best effect (Figure 2A)
The results showed that compared with MNNG group, the cell survival rate of 20 and 40 μM BBR co-culture with MNNG groups increased significantly (p < 0.01) (Figure 2B)
Summary
Gastric cancer (GC) is the second leading cause of cancer-related death worldwide (Hallowell et al, 2019; Liou et al, 2020). As a precancerous lesion of gastric cancer, CAG plays an important role in the occurrence and development of gastric cancer (Weck et al, 2007; Thapa et al, 2019). Treatment of CAG can effectively prevent the occurrence of GC and has important clinical significance. Modern medicine mostly uses non-specific treatment for CAG, including eradication of Helicobacter pylori, use of antacid and mucosal protective agents (Tian et al, 2019). The disease is easy to attack repeatedly and is difficult to cure. This seriously affects human health, and puts a huge burden on the health care system (Chen et al, 2019), so there is an urgent need to find new and effective therapeutic drugs
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