Wogonoside prevents colitis-associated colorectal carcinogenesis and colon cancer progression in inflammation-related microenvironment via inhibiting NF-κB activation through PI3K/Akt pathway.

Yang Sun,Xiaoping Wang,Na Lu,Wenjun Li,Youxiang Ding,Li Zhao,Lingyi Kong,Qinglong Guo,Yue Zhao

doi:10.18632/oncotarget.8815

Yang Sun, Xiaoping Wang + Show 7 more

Open Access

https://doi.org/10.18632/oncotarget.8815

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Journal: Oncotarget	Publication Date: Apr 18, 2016
Citations: 44	License type: cc-by

Affiliation: China Pharmaceutical University

Abstract

The inflammatory microenvironment has been reported to be correlated with tumor initiation and malignant development. In the previous studies we have found that wogonoside exerts anti-neoplastic and anti-inflammatory activities. In this study, we aimed to further investigate the chemopreventive effects of wogonoside on colitis-associated cancer and delineated the potential mechanisms. In the azoxymethane initiated and dextran sulfate sodium (AOM/DSS) promoted colorectal carcinogenesis mouse model, wogonoside significantly reduced the disease severity, lowered tumor incidence and inhibited the development of colorectal adenomas. Moreover, wogonoside inhibited inflammatory cells infiltration and cancer cell proliferation at tumor site. Furthermore, wogonoside dramatically decreased the secretion and expression of IL-1β, IL-6 and TNF-α as well as the nuclear expression of NF-κB in adenomas and surrounding tissues. In vitro results showed that wogonoside suppressed the proliferation of human colon cancer cells in the inflammatory microenvironment. Mechanistically, we found that wogonoside inhibited NF-κB activation via PI3K/Akt pathway. In conclusion, our results demonstrated that wogonoside attenuated colitis-associated tumorigenesis in mice and inhibited the progression of human colon cancer in inflammation-related microenvironment via suppressing NF-κB activation by PI3K/Akt pathway, indicating that wogonoside could be a promising therapeutic agent for colorectal cancer.

Highlights

Colorectal cancer (CRC) is the second commonest malignancy in the world with high mortality [1, 2]
Wogonoside was well tolerated in mice, and no observable toxicity and gross change in any organ examined in all groups up to 105 days (Table 1)
We found that IL-1β, IL-6 and TNF-α were expressed at relatively high levels in AOM/dextran sulfate sodium (DSS) model; wogonoside effectively suppressed the expression of IL-1β, IL-6 and TNF-α (Figure 3A and 3B)

Summary

Introduction

Colorectal cancer (CRC) is the second commonest malignancy in the world with high mortality [1, 2]. Increasing evidence has suggested that inflammation is correlated with in tumor initiation and malignant progression [3,4,5,6,7]. The primary producers of cytokines during inflammation, play key roles in the innate immune system and migrate to hypoxic sites such as growing tumor mass [13]. These cells in the tumor microenvironment promoted tumor initiation, accelerated tumor progression, angiogenesis and metastasis by releasing a variety of growth factors, chemokines and cytokines [11, 14,15,16,17]

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