Matrine Suppresses Arsenic-Induced Malignant Transformation of SV-HUC-1 Cells via NOX2

被引:2
作者
Wang, Lanfei [1 ,2 ,3 ]
Qiu, Nianfeng [1 ,2 ,3 ]
Tong, Suyuan [1 ,2 ,3 ]
Yu, Yan [1 ,2 ,3 ]
Xi, Shuhua [1 ,2 ,3 ]
Wang, Fei [1 ,2 ,3 ]
机构
[1] China Med Univ, Key Lab Environm Stress & Chron Dis Control & Prev, Minist Educ, Shenyang 110122, Peoples R China
[2] China Med Univ, Sch Publ Hlth, Dept Environm Hlth, Shenyang 110122, Peoples R China
[3] China Med Univ, Key Lab Liaoning Prov Tox & Biol Effects Arsen, Shenyang 110122, Peoples R China
基金
中国国家自然科学基金;
关键词
arsenic; bladder cancer; matrine; NADPH Oxidase 2; NLRP3; DRINKING-WATER; CANCER; DAMAGE; INFLAMMASOME; METASTASIS; EXPRESSION; APOPTOSIS; INVASION; GROWTH; RISK;
D O I
10.3390/ijms25168878
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Arsenic (As) has been classified as a carcinogen for humans. There is abundant evidence indicating that arsenic increases the risk of bladder cancer among human populations. However, the underlying mechanisms have yet to be fully understood and elucidated. NADPH oxidases (NOXs) are the main enzymes for ROS production in the body. NADPH Oxidase 2 (NOX2), which is the most distinctive and ubiquitously expressed subunit of NOXs, can promote the formation and development of tumors. The utilization of NOX2 as a therapeutic target has been proposed to modulate diseases resulting from the activation of NOD-like receptor thermal protein domain associated protein 3 (NLRP3). Matrine has been reported to exhibit various pharmacological effects, including anti-inflammatory, antifibrotic, antitumor, and analgesic properties. However, it has not been reported whether matrine can inhibit malignant transformation induced by arsenic in uroepithelial cells through NOX2. We have conducted a series of experiments using both a sub-chronic NaAsO2 exposure rat model and a long-term NaAsO2 exposure cell model. Our findings indicate that arsenic significantly increases cell proliferation, migration, and angiogenesis in vivo and in vitro. Arsenic exposure resulted in an upregulation of reactive oxygen species (ROS), NOX2, and NLRP3 inflammasome expression. Remarkably, both in vivo and in vitro, the administration of matrine demonstrated a significant improvement in the detrimental impact of arsenic on bladder epithelial cells. This was evidenced by the downregulation of proliferation, migration, and angiogenesis, as well as the expression of the NOX2 and NLRP3 inflammasomes. Collectively, these findings indicate that matrine possesses the ability to reduce NOX2 levels and inhibit the transformation of bladder epithelial cells.
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页数:18
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