Effect of Jianpi Jiedu Recipe on angiogenesis and the PTEN/PI3K/AKT signaling pathway in the course of Helicobacter pylori-induced gastric cancer in C57BL/6 mice

Abstract

Highlights Jianpi Jiedu Recipe can reduce the infection rate of Helicobacter pylori in mice gastric mucosa by inhibiting the expression of MVD and VEGF, and reducing the inactivation of PTEN. Editor’s Summary In addition to use triple antibiotics to treat the infection of Helicobacter pylori , Jianpi Jiedu Recipe can reduce the infection rate of Helicobacter pylori and further prevent the occurrence of gastric cancer. Objective: To reveal the effect of Jianpi Jiedu recipe (JPJDR) on angiogenesis and the PTEN (Phosphatase and tensin homolog deleted on chromosome ten)/PI3K/AKT signaling pathway in the course of H. pylori infection-induced carcinogenesis of gastric mucosa in C57BL/6 mice. Methods: Two-hundred C57BL/6 mice were randomly divided into five groups (control group, model group, JPJDR low-dose group, JPJDR medium-dose group, and JPJDR high-dose group), 40 in each group. A mouse model of gastric cancer, induced by H. pylori standard strain infection, was established. The mice of JPJDR low-dose, middle-dose, and high-dose groups were intragastrically administered 250, 500, and 1000 mg/kg JPJDR per day, respectively. After 72 weeks, the H. pylori infection in gastric mucosa of the mice was analyzed by rapid urease test; the pathological changes in the gastric mucosa of mice were assessed by histopathological examination, and micro-vessel density (MVD), vascular endothelial growth factor (VEGF), and PTEN/PI3K/AKT levels were determined. Results: The incidence of gastric cancer in each group (control group, model group, JPJDR low-dose, medium-dose, high-dose group) was 0%, 26.3%, 13.2%, 10%, and 7.5% respectively. The incidence of gastric cancer in the Chinese medicine group was significantly lower than that of the model group ( P = 0.020, P = 0.023, P = 0.007). The expression of MVD and VEGF in the model group was significantly higher than that in the control group ( P = 0.002, P < 0.001), while the expression of MVD and VEGF decreased in the Chinese medicine group. The expression of p-PTEN and p-AKT in the model group was significantly higher than that in the control group (All P < 0.001), while Chinese medicine could reduce the expression of p-PTEN and p-AKT to varying extents. Conclusion: Long-term infection of C57BL/6 mice with H. pylori induces gastric carcinogenesis, by increasing gastric mucosal MVD, promoting the expression of VEGF, inhibiting the activity of PTEN, and activating the PI3K/AKT signaling pathway. JPJDR can reduce the infection rate of H. pylori in mouse gastric mucosa, inhibit the expression of MVD and VEGF, and reduce the inactivation of PTEN.