Basic Study
Copyright ©The Author(s) 2016. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastrointest Oncol. Mar 15, 2016; 8(3): 305-313
Published online Mar 15, 2016. doi: 10.4251/wjgo.v8.i3.305
Expression of p-STAT3 and vascular endothelial growth factor in MNNG-induced precancerous lesions and gastric tumors in rats
Xiao-Yan Wang, Lou-Lei Wang, Xuan Zheng, Li-Na Meng, Bin Lyu, Hai-Feng Jin
Xiao-Yan Wang, Lou-Lei Wang, the First Affiliated Hospital of Zhejiang University, Hangzhou 310003, Zhejiang Province, China
Xuan Zheng, Li-Na Meng, Bin Lyu, Hai-Feng Jin, the First Affiliated Hospital of Zhejiang Chinese Medicine University, Hangzhou 310006, Zhejiang Province, China
Author contributions: Wang XY and Wang LL are co-first authors; they contributed equally to the work; Zheng X, Meng LN, Lyu B and Jin HF contributed to the conception and design of the study, acquisition, analysis and interpretation of data; all authors drafted the article and made critical revisions related to the intellectual content of the manuscript, and approved the final version of the article to be published.
Institutional animal care and use committee statement: The Animal Care and Use Committee of the First Affiliated Hospital of Zhejiang Chinese Medicine University approved the protocol.
Conflict-of-interest statement: To the best of our knowledge, no conflict of interest exists.
Data sharing statement: No additional data are available.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Correspondence to: Hai-Feng Jin, MD, Resident Physician of Gastroenterology, the First Affiliated Hospital of Zhejiang Chinese Medicine University, Youdian Rd. 54, Hangzhou 310006, Zhejiang Province, China. jinhaifeng0908@163.com
Telephone: +86-571-87077785 Fax: +86-571-87077785
Received: June 16, 2015
Peer-review started: June 19, 2015
First decision: October 21, 2015
Revised: November 14, 2015
Accepted: January 21, 2016
Article in press: January 22, 2016
Published online: March 15, 2016
Processing time: 264 Days and 13.6 Hours
Abstract

AIM: To investigate the dynamic expression of p-signal transducer and activator of transcription 3 (STAT3) and vascular endothelial growth factor (VEGF) in the formation of gastric tumors induced by drinking water containing N-methyl-N’-nitro-N-nitrosoguanidine (MNNG) in Wistar rats.

METHODS: One hundred and twenty Wistar rats were randomly divided into two groups (60 in each group): Control group and Model group. The rats in each group were then randomly divided into three groups (20 in each group): C/M15, C/M25 and C/M40 (15, 25 and 40 represent the number of feeding weeks from termination). Rats in the control group received normal drinking water and rats in the model group received drinking water containing 100 μg/mL MNNG. Stomach tissues were collected at the end of the 15th, 25th and 40th week, respectively, for microscopic measurement using hematoxylin and eosin staining. The expression of p-STAT3 and VEGF in different pathological types of gastric tissue, including normal, inflammation, atrophy, hyperplasia and gastric stromal tumor, was observed by immunohistochemistry and Western blot, and the corelation between p-STAT3 and VEGF was analyzed.

RESULTS: (1) The expression of p-STAT3 in tissue with gastritis, atrophy, dysplasia and gastric stromal tumor were significantly increased in the model group compared with the control group (2.5 ± 1.0, 2.75 ± 0.36, 6.2 ± 0.45, 5.67 ± 0.55 vs 0.75 ± 0.36, P = 0.026, 0.035, 0.001, 0.002, respectively); the expression of p-STAT3 in tissue with dysplasia was higher than that in samples with gastritis or atrophy (6.2 ± 0.45 vs 2.5 ± 1.0, P = 0.006; 6.2 ± 0.45 vs 2.75 ± 0.36, P = 0.005, respectively); however, the expression of p-STAT3 in gastritis and atrophy was not significantly different (P > 0.05); (2) the expression of VEGF in tissue with gastritis, atrophy, dysplasia and gastric stromal tumor was significantly increased in the model group compared with normal gastric mucosa; and the expression of VEGF in tissue with dysplasia was higher than that in tissue with inflammation and atrophy (10.8 ± 1.96 vs 7.62 ± 0.25, P = 0.029; 10.8 ± 1.96 vs 6.26 ± 0.76, P = 0.033, respectively); similarly, the expression of VEGF in tissue with gastritis and atrophy was not significantly different (P > 0.05); and (3) the expression of VEGF was positively correlated with p-STAT3.

CONCLUSION: p-STAT3 plays an important role in gastric cancer formation by regulating the expression of VEGF to promote the progression of gastric tumor from gastritis.

Keywords: Wistar rat; Precancerous gastric lesions; Gastric tumor; Vascular endothelial growth factor; p-signal transducer and activator of transcription 3; N-methyl-N’-nitro-N-nitrosoguanidine

Core tip: The results show that signal transducer and activator of transcription 3 (STAT3) is partially responsible for the progression from chronic gastritis to gastric carcinoma induced by N-methyl-N’-nitro-N-nitrosoguanidine (MNNG) and is significantly related to the expression of vascular endothelial growth factor (VEGF) during this process. It is considered that STAT3 induces an abnormal level of VEGF expression to promote the formation of gastric carcinoma. To the best of our knowledge, this is the first report to show that p-STAT3 is persistently activated during the progression of chronic gastritis to gastritis carcinoma induced by the administration of MNNG in rats, and was positively associated with the expression of VEGF.