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Traditional Medicine Research  2018, Vol. 3 Issue (1): 29-39    DOI: 10.12032/TMR201809062
Empirical Formula Research     
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
Ning-Ning Liu1, Wan-Li Deng1, Chao-Jun Wu1, Yuan-Yuan Feng1, Xin-Wen Ma1, Qi Li1,*()
1Department of Oncology, Shuguang Hospital, Shanghai University of Traditional Chinese Medicine, Cancer Institute of Integrative Medicine, Shuguang Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China.
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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.

Abstract

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.



Key wordsHelicobacter pylori      Gastric cancer      PTEN/PI3K/AKT      Vascular endothelial growth factor     
Published: 05 January 2018
Fund:  This study was supported by National Natural Science Foundation of China (81202663,81273958), the Natural Science Foundation of Shanghai, China (12ZR1449300), the Shanghai Health and Family Planning Commission (20134309);Program for Outstanding Academic Leader of Shanghai, Program for Outstanding Medical Academic Leader of Shanghai, the Xinglin Star Plan of Shanghai (ZY3-RCPY-2-2006)
Corresponding Authors: Li Qi     E-mail: lzwf@hotmail.com
Cite this article:

Ning-Ning Liu, Wan-Li Deng, Chao-Jun Wu, Yuan-Yuan Feng, Xin-Wen Ma, Qi Li. 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. Traditional Medicine Research, 2018, 3(1): 29-39. doi: 10.12032/TMR201809062

URL:

https://www.tmrjournals.com/tmr/EN/10.12032/TMR201809062     OR     https://www.tmrjournals.com/tmr/EN/Y2018/V3/I1/29

Groups No. H.pylori positive rate (%)(No.)
Control group 40 0 (0)
Model group 38 100 (38)a
Low dose JPJDR group 38 8 (3)b
Medium dose JPJDR group 40 0 (0)c
High dose JPJDR group 40 0 (0)d
Table 1 Gastric mucosa H.pylori colonization at 72 weeks
Groups No. Incidence of gastric cancer (%) (No.)
Control group 40 0 (0)
Model group 38 26.3 (10)a
Low dose JPJDR group 38 13.2 (5)b
Medium dose JPJDR group 40 10 (4)c
High dose JPJDR group 40 7.5 (3)d
Table 2 The incidence of gastric cancer at 72 weeks
Groups MVD
Control group 4.5 ± 3.6
Model group 50.2 ± 4.2a
Low dose JPJDR group 22.3 ± 3.5b
Medium dose JPJDR group 15.2 ± 3.8c
High dose JPJDR group 6.5 ± 3.9d
Table 3 Effect of JPJDR on gastric mucosal MVD ($bar{x}$±s) in C57BL/6 mice infected with H. pylori
Figure 1 Gastric mucosal MVD in C57BL/6 mice
Groups IOD
Control group 658.5 ± 328.9
Model group 5208.2 ± 421.1a
Low dose JPJDR group 3315.2 ± 461.35b
Medium dose JPJDR group 2125.1 ± 359.2c
High dose JPJDR group 1689.5 ± 400.2d
Table 4 Effect of JPJDR on gastric mucosal VEGF ($bar{x}$±s) in C57BL/6 mice infected with H. pylori
Figure 2 Expression of VEGF in gastric mucosa of C57BL/6 mice
Figure 3 Expression of PTEN protein in gastric mucosa of C57BL/6 mice
Figure 4 Expression of p-PTEN protein in gastric mucosa of C57BL/6 mice
Groups PTEN (IOD) p-PTEN (IOD)
Control group 16025.5 ± 852.6 256.6 ± 166.2
Model group 15926.6 ± 759.9a 12569.5 ± 339.5e
Low dose JPJDR group 16159.2 ± 812.5b 5650.3 ± 316.6f
Medium dose JPJDR group 16105.9 ± 886.9c 4526.2 ± 252.7g
High dose JPJDR group 15835.9 ± 795.4d 2362.7 ± 195.1h
Table 5 Expression of p-PTEN, PTEN protein in gastric mucosa of C57BL/6 mice ($bar{x}$± s)
Figure 5 Expression of AKT protein in gastric mucosa of C57BL/6 mice
Figure 6 Expression of p-AKT protein in gastric mucosa of C57BL/6 mice
Groups AKT p-AKT
Control group 15369.6 ± 1386.6 312.5 ± 126.5
Model group 15508.2 ± 1425a 5236.3 ± 365.6e
Low dose JPJDR group 15215.9 ± 1401.5b 3512.2 ± 286.3f
Medium dose JPJDR group 15352.8 ± 1360.5c 2563.9 ± 262.3g
High dose JPJDR group 15412.2 ± 1405.6d 1526.3 ± 159.9h
Table 6 Expression of AKT, p-AKT protein in gastric mucosa of C57BL/6 mice ($bar{x}$±s)
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