Celastrus Orbiculatus Extracts Inhibit the Metastasis through Attenuating PI3K/Akt/mTOR Signaling Pathway in Human Gastric Cancer.

Rapamycin receptor inhibitors have been applied in the clinic and achieved satisfactory therapeutic effect recently. The mechanisms did not clearly show how the Celastrus Orbiculatus Extracts (COE) inhibited the expression of the mammalian Target of Rapamycin (mTOR) in human gastric cancer cells. The aim of this study was to investigate whether the COE inhibited the metastasis through the mTOR signaling pathway in human gastric cancer MGC-803 cells. The abnormal expression level of mTOR protein was detected by immunohistochemistry in human gastric cancer tissue. The MGC-803/mTOR- cells were constructed by knockdown of mTOR using lentivirus infection technique. The human gastric cancer MGC-803/mTOR- cells were treated with different concentrations (20, 40, 80 μg/ml) of COE for 24 hours. The ability of cell metastasis was analyzed by the cell invasion and migration assay. The expression levels of PI3K/Akt/mTOR signaling pathway were detected by Western Blotting. COE inhibited the proliferation, invasion and migration of MGC-803/mTOR- cells in a concentrationdependent manner. The expression of E-cadherin protein increased, and the expression of N-cadherin and Vimentin decreased simultaneously in the MGC-803/mTOR- cells. 4EBP1, p-4EBP1, P70S6k, p-P70S6k, mTOR, p-mTOR, PI3K and Akt proteins in MGC-803/mTOR- cells were reduced in a dose-dependent manner. COE could not only inhibit cell growth, invasion and migration, but also inhibit the epithelialmesenchymal transition of gastric cancer cells. The molecular mechanism of COE inhibited the metastasis which may be related to the PI3K/Akt/mTOR signal pathway. This study provides ideas for the development of new anti-gastric cancer drugs.

Qian Y ，Yan Y ，Lu H ，Zhou T ，Lv M ，Fang C ，Hou J ，Li W ，Chen X ，Sun H ，Li Y ，Wang Z ，Zhao N ，Gu Y ，Ding Y ，Liu Y ... -  《-》

Celastrus orbiculatus Extracts Inhibit Human Hepatocellular Carcinoma Growth by Targeting mTOR Signaling Pathways.

Qian YY ，Li WY ，Yan Y ，Zhao XY ，Yang T ，Fang CC ，Hou JJ ，Liu YQ ... -  《-》

Celastrus orbiculatus extracts induce apoptosis in mTOR-overexpressed human hepatocellular carcinoma HepG2 cells.

Qian Y ，Yang T ，Zhao X ，Yan Y ，Li W ，Fang C ，Hou J ，Tao L ，Liu Y ... -  《BMC Complementary and Alternative Medicine》

Anticancer efficacy of the ethyl acetate extract from the traditional Chinese medicine herb Celastrus orbiculatus against human gastric cancer.

The traditional Chinese medicine (TCM) herb Celastrus orbiculatus is an important folk medicinal plant in China that has been used as an anti-inflammatory, antitumor, and analgesic in various diseases. The ethyl acetate extract of C. orbiculatus (C. orbiculatus extract, COE) was reported to show significant antitumor effects. However, no study in China or abroad has reported the effect and mechanism of COE in triggering apoptosis of gastric cancer (GC) cells. To further uncover the molecular mechanism underlying COE's apoptotic and anti-proliferative effects and lay a foundation for the development of novel, effective antitumor TCM agents. The effect of COE on AGS and BGC-823 GC cell viability was examined using a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Apoptosis of AGS and BGC-823 cells induced by COE was analyzed using flow cytometry and a mitochondrial membrane potential assay kit (JC-1). The proliferating GC cells were identified and examined using a 5-bromo-2'-deoxyuridine (BrdU) staining kit and flow cytometric analysis. A western blot assay was used to detect the effect of COE on apoptosis-related proteins, B-cell lymphoma-2 (Bcl-2), Bcl-extra-large (Bcl-xL), Bcl-2-like protein 12 (Bcl-L12), Bcl-2-associated X protein (Bax), and caspase as well as proliferation-related proteins, phosphoinositide 3-kinase (PI3K)/Akt/mechanistic target of rapamycin (mTOR)/p70s6k. Transmission electron microscopy (TEM) and an animal imaging technique were used to evaluate the microstructure of apoptotic GC cells and the effect of COE on tumor cell growth in vivo, respectively. The results indicate that COE significantly inhibited proliferation and induced apoptosis of GC AGS and BGC-823 cell lines both in vivo and in vitro. COE significantly decreased the cell mitochondrial membrane potential. Moreover, COE downregulated the levels of Bcl-2, Bcl-xL, and PI3K/Akt/mTOR/p70s6k while those of Bax and caspase were upregulated. More interestingly, COE altered the microstructure of the mitochondria. All these data collectively indicate that COE not only has significant antiproliferative effects but also has both in vivo and in vitro apoptotic effects. In addition, COE altered the structure and function of the mitochondria, which is another potential pathway for the antitumor activity of COE. These findings may provide a basis for the development of new anticancer TCM candidates.

Wang H ，Tao L ，Ni T ，Gu H ，Jin F ，Dai X ，Feng J ，Ding Y ，Xiao W ，Guo S ，Hisamitsu T ，Qian Y ，Liu Y ... -  《-》

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》