Ginsenoside Rb2 inhibits epithelial-mesenchymal transition of colorectal cancer cells by suppressing TGF-β/Smad signaling

被引：66
作者：
Dai Guoliang [1 ]
Sun Bingting [2 ]
Gong Tao [3 ]
Pan Zihao [4 ]
Meng Qinghai [4 ]
Ju Wenzheng [1 ]
机构：
[1] Nanjing Univ Chinese Med, Dept Clin Pharmacol, Affiliated Hosp, Nanjing 210029, Jiangsu, Peoples R China
[2] Nanjing Univ Chinese Med, TCM Res Inst, Affiliated Hosp 3, Nanjing 210001, Jiangsu, Peoples R China
[3] Nanjing Univ Chinese Med, Dept Oncol, Affiliated Hosp 3, Nanjing 210001, Jiangsu, Peoples R China
[4] Nanjing Univ Chinese Med, Sch Pharm, Nanjing 210023, Jiangsu, Peoples R China
来源：
PHYTOMEDICINE | 2019年 / 56卷
基金：
中国国家自然科学基金;
关键词：
Ginsenoside Rb2; Epithelial-mesenchymal transition; TGE-beta; 1; Colorectal cancer; BETA; METASTASIS; EXPRESSION; ADHESION;
D O I：
10.1016/j.phymed.2018.10.025
中图分类号：
Q94 [植物学];
学科分类号：
071001 ;
摘要：
Background: Treating colorectal cancer (CRC) continues to be a clinical challenge. Studies have shown that epithelial-mesenchymal transition (EMT) is a critical step in tumor progression and transforming growth factor-beta 1 (TGF-beta 1) signaling has been shown to play a crucial role in EMT. Here, we investigate the inhibition effect of Ginsenoside Rb2, main bioactive component of ginseng, in human colorectal cancer cells via TGF-beta 1. Purpose: The current study aims to study the inhibitory effect of Ginsenoside Rb2 on HCT116 and SW620 cells and its anti-tumor mechanism. Methods: Histomorphological analysis and western blot analysis were performed to evaluate expression of TGF-beta 1 in human cancerous colon samples and the adjacent normal samples. The docking simulation assay were performed to explore the potential mode of binding of Ginsenoside Rb2 to the TGF-beta 1 protein. CCK8, adhesion and invasion assay were used to assess the effects of Ginsenoside Rb2 in HCT116 and SW620 cells. RT-PCR, Western blot and Immunohistochemical staining were employed to detect the TGF-beta 1-related signaling pathways in the colon cancer cells and/or xenograft mice. Results: The expression of TGF-beta 1 in human cancerous colon samples was significantly increased compared with the adjacent normal samples. Ginsenoside Rb2 inhibit the growth, adhesion, EMT and metastasis of human colorectal cancer cells. The docking simulation assay confirmed that Ginsenoside Rb2 bound to the hydrophobic pocket of TGF-beta 1, which partially overlaps with the binding sites on TGF-beta 1, and thus disrupted TGF-beta 1 dimerization. Western Blot analysis further confirmed that Ginsenoside Rb2 could inhibit the expression of TGF-beta 1 in vitro and in vivo. Furthermore, Ginsenoside Rb2 could inhibit the expression of Smad4 and phosphorylated Smad2/3. Conclusion: Ginsenoside Rb2 could inhibit EMT of colorectal cancer cells through the TGF-beta 1/Smad signaling, and might be a potential candidate for the treatment of colorectal cancer.
引用
收藏
页码：126 / 135
页数：10
相关论文
共 31 条
[1]   Ginseng pharmacology - Multiple constituents and multiple actions [J].
Attele, AS ;
Wu, JA ;
Yuan, CS .
BIOCHEMICAL PHARMACOLOGY, 1999, 58 (11) :1685-1693
[2]   Inhibition of TGF-β with neutralizing antibodies prevents radiation-induced acceleration of metastatic cancer progression [J].
Biswas, Swati ;
Guix, Marta ;
Rinehart, Cammie ;
Dugger, Teresa C. ;
Chytil, Anna ;
Moses, Harold L. ;
Freeman, Michael L. ;
Arteaga, Carlos L. .
JOURNAL OF CLINICAL INVESTIGATION, 2007, 117 (05) :1305-1313
[3]  
Chang Yuan S, 2003, Integr Cancer Ther, V2, P13, DOI 10.1177/1534735403251167
[4]   Ginsenoside Rb2 inhibits osteoclast differentiation through nuclear factor-kappaB and signal transducer and activator of transcription protein 3 signaling pathway [J].
Cong, Fei ;
Liu, Jian ;
Wang, Chunmei ;
Yuan, Zhi ;
Bi, Long ;
Liang, Jidong ;
Su, Ke ;
Qiu, Yucheng ;
Song, Tao ;
Fan, Jinzhu ;
Chao, Gao .
BIOMEDICINE & PHARMACOTHERAPY, 2017, 92 :927-934
[5]   Colorectal cancer [J].
Cunningham, David ;
Atkin, Wendy ;
Lenz, Heinz-Josef ;
Lynch, Henry T. ;
Minsky, Bruce ;
Nordlinger, Bernard ;
Starling, Naureen .
LANCET, 2010, 375 (9719) :1030-1047
[6]   Genetics, diagnosis and management of colorectal cancer [J].
De Rosa, Marina ;
Pace, Ugo ;
Rega, Daniela ;
Costabile, Valeria ;
Duraturo, Francesca ;
Izzo, Paola ;
Delrio, Paolo .
ONCOLOGY REPORTS, 2015, 34 (03) :1087-1096
[7]  
Fischer Andrew H, 2008, CSH Protoc, V2008, DOI 10.1101/pdb.prot4986
[8]  
Fujimoto J, 2001, EUR J GYNAECOL ONCOL, V22, P339
[9]   Survival of patients with advanced colorectal cancer improves with the availability of fluorouracil-leucovorin, irinotecan, and oxaliplatin in the course of treatment [J].
Grothey, A ;
Sargent, D ;
Goldberg, RM ;
Schmoll, HJ .
JOURNAL OF CLINICAL ONCOLOGY, 2004, 22 (07) :1209-1214
[10]   The density of macrophages in colorectal cancer is inversely correlated to TGF-β1 expression and patients' survival [J].
Gulubova, Maya ;
Ananiev, Julian ;
Yovchev, Yovchev ;
Julianov, Aleksander ;
Karashmalakov, Anatoli ;
Vlaykova, Tatyana .
JOURNAL OF MOLECULAR HISTOLOGY, 2013, 44 (06) :679-692
1234