Wumei Pill Ameliorates AOM/DSS-Induced Colitis-Associated Colon Cancer through Inhibition of Inflammation and Oxidative Stress by Regulating S-Adenosylhomocysteine Hydrolase- (AHCY-) Mediated Hedgehog Signaling in Mice

被引：17

作者：

Wang, Jue ^{[1
]}

Ding, Kang ^{[2
]}

Wang, Yuhang ^{[1
]}

Yan, Tingdong ^{[1
]}

Xu, Yun ^{[1
]}

Deng, Zirong ^{[1
]}

Lin, Weiling ^{[1
]}

Zhang, Libei ^{[1
]}

Zhu, Weizhong ^{[1
]}

Zhao, Rui ^{[1
]}

Zhou, Yuhang ^{[1
]}

Liu, Zhaoguo ^{[1
]}

机构：

[1] Nantong Univ, Sch Pharm, 19 Qixiu Rd, Nantong 226001, Jiangsu, Peoples R China

[2] Nanjing Univ Chinese Med, Natl Ctr Colorectal Surg, Jiangsu Integrate Colorectal Oncol Ctr, Nanjing Hosp Chinese Med, Nanjing 210022, Peoples R China

来源：

OXIDATIVE MEDICINE AND CELLULAR LONGEVITY | 2022年 / 2022卷

基金：

中国国家自然科学基金; 中国博士后科学基金;

关键词：

TRADITIONAL CHINESE MEDICINE; TUMORIGENESIS; ANGIOGENESIS; METASTASIS; INDUCTION; PATHWAY; GROWTH; DZNEP;

D O I：

10.1155/2022/4061713

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

Wumei Pill (WMP) is a traditional Chinese herbal formulation and widely used to treat digestive system diseases in clinical. S-Adenosylhomocysteine hydrolase (AHCY) can catalyze the hydrolysis of S-adenosylhomocysteine to adenosine and homocysteine in living organisms, and its abnormal expression is linked to the pathogenesis of many diseases including colorectal cancer (CRC). A previous study reported that WMP could prevent CRC in mice; however, the underlying mechanisms especially the roles of AHCY in WMP-induced anti-CRC remain largely unknown. Here, we investigated the regulatory roles and potential mechanisms of AHCY in WMP-induced anti-CRC. WMP notably alleviated the azoxymethane/dextran sulfate sodium- (AOM/DSS-) induced colitis-associated colon cancer (CAC) in mice. Besides, WMP inhibited the inflammation and oxidative stress in AOM/DSS-induced CAC mice. AHCY was high expression in clinical samples of colon cancer compared to the adjacent tissues. WMP inhibited the AHCY expression in AOM/DSS-induced CAC mice. An in vitro study found that AHCY overexpression induced cell proliferation, colony formation, invasion, and tumor angiogenesis, whereas its knockdown impaired its oncogenic function. AHCY overexpression enhanced, while its knockdown weakened the inflammation and oxidative stress in colon cancer cells. Interestingly, WMP potently suppressed the hedgehog (Hh) signaling in AOM/DSS-induced CAC mice. A further study showed that AHCY overexpression activated the Hh signaling while AHCY knockdown inactivated the Hh signaling. Moreover, activation of the Hh signaling reversed the effect of AHCY silencing on inflammation and oxidative stress in vitro. In conclusion, WMP alleviated the AOM/DSS-induced CAC through inhibition of inflammation and oxidative stress by regulating AHCY-mediated hedgehog signaling in mice. These findings uncovered a potential molecular mechanism underlying the anti-CAC effect of WMP and suggested WMP as a promising therapeutic candidate for CRC.

引用

页数：28