Antimetastatic effects of Celastrus orbiculatus on human gastric adenocarcinoma by inhibiting epithelial-mesenchymal transition and NF-κB/snail signaling pathway.
OBJECTIVE
Celastrus orbiculatus has been used as a folk medicine in China for the treatment of many diseases. In the laboratory, the ethyl acetate extract of Celastrus orbiculatus (COE) displays a wide range of anticancer functions. However, the inhibition of the metastasis mechanism of COE in gastric cancer cells has not been investigated so far. The present study was undertaken to determine if the antimetastatic effects of COE were involved in inhibition of the epithelial-mesenchymal transition (EMT) of human gastric adenocarcinoma SGC-7901 cells.


METHODS
The adhesion, invasion, and migration of SGC-7901 cells were determined by COE treatment in vitro, using Matrigel-coated plate, transwell membrane chamber, and wound healing models, respectively. In vivo, the growth-inhibiting and antimetastatic effects of COE on the nude mice model of gastric cancer were tested and the mechanisms were explored. The expression of EMT markers and nuclear factor κB (NF-κB)/Snail signaling pathway were evaluated by using western blotting and immunohistochemistry.


RESULTS
Treatment with COE dose-dependently inhibited the proliferation, adhesion, invasion, and migration of SGC-7901 cells in vitro, which was realized by enhancing the expression of E-cadherin and reducing N-cadherin and vimentin expression. Moreover, COE suppressed the activation of NF-κB/Snail signaling pathway induced by tumor necrosis factor-α. In addition, COE effectively suppressed tumor growth and metastasis in the nude mice model due to reduced expression of N-cadherin, vimentin, NF-κB p65, and Snail and increased expression of E-cadherin in the tumor tissues.


CONCLUSIONS
Our findings provided new evidence that COE is an effective inhibitor of metastatic potential of SGC-7901 cells through suppression of EMT and NF-κB/Snail signal pathway. Based on these findings, COE may be considered a novel anticancer agent for the treatment of metastasis in gastric cancer.
Yangzhou University, Yangzhou, Jiangsu, China.
Yaodong
Y
Zhu
Yangzhou University, Yangzhou, Jiangsu, China liuyanqing2014@163.com.
Yanqing
Y
Liu
Yangzhou University, Yangzhou, Jiangsu, China.
Yayun
Y
Qian
Yangzhou Traditional Chinese Medicine Hospital, Yangzhou, Jiangsu, China.
Xiaojun
X
Dai
Yangzhou University, Yangzhou, Jiangsu, China.
Lin
L
Yang
Yangzhou University, Yangzhou, Jiangsu, China.
Jue
J
Chen
Showa University, Tokyo, Japan.
Shiyu
S
Guo
Showa University, Tokyo, Japan.
Tadashi
T
Hisamitsu
D000230:Adenocarcinoma / Q000188:drug therapy* / Q000378:metabolism; D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000627:therapeutic use*; D031247:Celastrus / Q000737:chemistry*; D045744:Cell Line, Tumor; D000529:Complementary Therapies / Q000379:methods; D058750:Epithelial-Mesenchymal Transition / Q000187:drug effects*; D006801:Humans; D008297:Male; D008516:Medicine, Chinese Traditional / Q000379:methods; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D023421:Models, Animal; D016328:NF-kappa B / Q000378:metabolism; D009362:Neoplasm Metastasis / Q000517:prevention & control*; D000071250:Snail Family Transcription Factors; D013274:Stomach Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D014157:Transcription Factors / Q000378:metabolism
D000972:Antineoplastic Agents, Phytogenic; D016328:NF-kappa B; D000071250:Snail Family Transcription Factors; D014157:Transcription Factors
Celastrus orbiculatus; antimetastasis; epithelial–mesenchymal transition; gastric cancer; nuclear factor κB