Celastrus orbiculatus Thunb. extract inhibits EMT and metastasis of gastric cancer by regulating actin cytoskeleton remodeling.

The traditional Chinese medicine herb Celastrus orbiculatus Thunb. is an important folk medicinal plant in China that has been used as an anti-inflammatory, antitumor, and analgesic in various diseases. Recent years, many studies have reported the significant effects of Celastrus orbiculatus Thunb. extract (COE) on gastric cancer. However, the specific mechanism by which COE regulates gastric cancer cytoskeleton remodeling and thus inhibits EMT has not yet been reported. To study the effect and mechanism of COE in inhibiting the epithelial-mesenchymal transition (EMT) and metastasis of gastric cancer cells, laying an experimental foundation for the clinical application and further development of COE. The high-content cell dynamic tracking system was used to continuously track the trajectory of cell movement in real time. Through the high-content data, the average movement distance and movement speed of the cells are calculated. Additionally, the dynamic images of the cell movement in the high-content imaging system are derived to analyze the impact of COE on the movement of gastric cancer cells. Cytoskeleton staining experiment was performed to detect the effect of COE on the assembly of gastric cancer cell cytoskeleton proteins. Western blot was employed to detect the changes of EMT and metastasis-related proteins in the gastric cancer cells treated by COE. The effect of COE on the key regulatory protein Cofilin-1 (CFL1) of cell movement was examined by Western blot and protein degradation experiment. The effect of COE on EMT and metastasis of the gastric cancer cells lacking CFL1 was assessed by a transwell assay. The in vivo inhibitory effect of COE on EMT and metastasis of gastric cancer was determined by the animal living image system. IHC assays were used to detect the levels of EMT-related proteins in COE reversal in vivo. The results showed that the movement distance and average movement speed of gastric cancer cells after COE treatment were significantly lower than those of the control group. Cytoskeleton staining experiments revealed that COE can significantly change the distribution of skeletal proteins in gastric cancer cells. Additionally, COE treatment significantly reduced the expression of Matrix metalloproteinases (MMP-2, MMP-9) and other proteins. Furthermore, COE can significantly accelerate the degradation of CFL1 protein, and both COE treatment and CFL1 deletion can significantly inhibit EMT and metastasis of gastric cancer cells. Lastly, the number of peritoneal metastases of gastric cancer cells was significantly reduced in animals after COE treatment. COE can reverse the levels of EMT-related proteins while reducing the expression levels of CFL1 protein in vivo. COE can significantly inhibit EMT and metastasis of gastric cancer cells in vivo and in vitro. This effect may be achieved by reducing the stability of CFL1 and inhibiting the assembly of actin in gastric cancer cells.

Wang H ，Luo Y ，Ou S ，Ni T ，Chu Z ，Feng X ，Dai X ，Zhang X ，Liu Y ... -  《-》

Triptonoterpene, a Natural Product from Celastrus orbiculatus Thunb, Has Biological Activity against the Metastasis of Gastric Cancer Cells.

Wang H ，Luo Y ，Hu Y ，Feng X ，Feng J ，Chu Z ，Ou S ，Dai X ，Wang X ，Liu Y ... -  《MOLECULES》

Research on the efficacy of Celastrus Orbiculatus in suppressing TGF-β1-induced epithelial-mesenchymal transition by inhibiting HSP27 and TNF-α-induced NF-κ B/Snail signaling pathway in human gastric adenocarcinoma.

Zhu Y ，Liu Y ，Qian Y ，Dai X ，Yang L ，Chen J ，Guo S ，Hisamitsu T ... -  《BMC Complementary and Alternative Medicine》

Celastrus orbiculatus Extract Inhibits the Invasion and Migration of Human Gastric Cancer Cells in the Hypoxia Microenvironment.

Gastric cancer is a common global disease. So far, the best choice for diagnosis and treatment of gastric cancer includes surgical resection, chemotherapy, and other targeted drug therapies; however, the overall survival rate of patients with gastric cancer is still very low. The hypoxic microenvironment facilitates tumor cells to develop tolerance to chemotherapy and radiotherapy and promotes the early invasion and metastasis of various tumors. Celastrus Orbiculatus extract (COE) has shown inhibitory activities against a variety of tumor cells. In this study, we found that COE could inhibit the invasion and migration of gastric cancer cells by inhibiting epithelial-mesenchymal transformation (EMT) in the hypoxia microenvironment. CoCl2 was first diluted to various concentrations and then used to treat MKN28 and AGS cells. The MTT (thiazolyl blue) assay was used to evaluate cell proliferation. The transwell assay was used to measure the invasion and migration abilities of the cells. Wound healing assays were used to detect the healing ability of the cells. Western blotting was used to assess the effects of COE on the expression of EMT and matrix metalloproteinase (MMP) signaling pathway-related proteins. We found that gastric cancer cells showed stronger proliferation, invasion, and metastasis in the hypoxia microenvironment. COE inhibited the migration and invasion of AGS and MKN28 cells in both hypoxic and normoxic environments. Additionally, COE decreased the expression of EMT and MMP signaling pathway-related proteins in gastric cancer cells. Therefore, it can be concluded that COE suppresses the migration and invasion of gastric cancer cells by inhibiting EMT and MMP in the hypoxia microenvironment.

Feng G ，Chu Z ，Wang H ，Liu Y ，Zhu F ... -  《-》

Celastrus orbiculatus extract suppresses the epithelial-mesenchymal transition by mediating cytoskeleton rearrangement via inhibition of the Cofilin 1 signaling pathway in human gastric cancer.

Wang H ，Gu H ，Feng J ，Qian Y ，Yang L ，Jin F ，Wang X ，Chen J ，Shi Y ，Lu S ，Zhao M ，Liu Y ... -  《-》