Ginkgolic Acid, a SUMO-1 Inhibitor, Inhibits the Progression of Oral Squamous Cell Carcinoma by Alleviating SUMOylation of SMAD4

被引:32
|
作者
Liu, Ke [1 ]
Wang, Xinhuan [1 ]
Li, Duo [1 ]
Xu, Dongyang [1 ]
Li, Dezhi [1 ]
Lv, Zhiyong [1 ]
Zhao, Dan [3 ]
Chu, Wen-Feng [2 ]
Wang, Xiao-Feng [1 ]
机构
[1] Harbin Med Univ Harbin, Dept Oral & Maxillofacial Surg, Affiliated Hosp 2, Harbin 150081, Heilongjiang, Peoples R China
[2] Harbin Med Univ Harbin, State Prov Key Labs Biomed Pharmaceut China, Dept Pharmacol, Minist Educ,Key Lab Cardiovasc Res,Coll Pharm, Harbin 150081, Heilongjiang, Peoples R China
[3] Harbin Med Univ Harbin, Affiliated Hosp 2, Dept Clin Pharm, Key Labs,Educ Minist Myocardial Ischemia Mech & T, Harbin 150081, Heilongjiang, Peoples R China
来源
MOLECULAR THERAPY-ONCOLYTICS | 2020年 / 16卷
基金
中国国家自然科学基金;
关键词
TUMOR-SUPPRESSOR GENE; TGF-BETA; PANCREATIC-CANCER; BILOBA; HEAD; OVEREXPRESSION; TRANSITIONS; EXPRESSION; INDUCTION; APOPTOSIS;
D O I
10.1016/j.omto.2019.12.005
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Small ubiquitin-related modifiers (SUMO) represent a class of ubiquitin-like proteins that are conjugated, like ubiquitin, by a set of enzymes to form cellular regulatory proteins, and play key roles in the control of cell proliferation, differentiation, and apoptosis. We found that ginkgolic acid (GA) can significantly reduce cell vitality in a dose- and time-dependent manner and can also accelerate cyto-apoptosis in both Tca8113 and Cal-27 cells. Migration and wound-healing assays were executed to determine the anti-migration effect of GA in oral squamous cell carcinoma (OSCC) cell lines. GA represses transforming growth factor-beta 1 (TGF-beta 1)-induced epithelial-mesenchymal transition (EMT) markers in OSCC cell lines. This investigation is the first evidence that GA suppresses TGF-beta 1-induced SUMOylation of SMAD4. We show that GA affects the phosphorylation of SMAD2/3 protein and the release of SMAD4. In the xenograft mouse model, the OSCC progression was reduced by GA, effectively suppressing the growth of tumors. In addition, siSMAD4 improved cell migration and viability, which was inhibited by GA in Tca8113 cells. GA suppresses tumorigenicity and tumor progression of OSCC through inhibition of TGF-beta 1-induced enhancement of SUMOylation of SMAD4. Thus, GA could be a promising therapeutic for OSCC.
引用
收藏
页码:86 / 99
页数:14
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