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

Author(s):

Yayun Qian*, Yan Yan, Hongmei Lu, Tingting Zhou, Mengying Lv, Chuanci Fang, Jingjing Hou, Wenyuan Li, Xiwen Chen, Hui Sun, Yajuan Li, Zheng Wang, Nan Zhao, Yajuan Gu, Yongling Ding* and Yanqing Liu*   Pages 1754 - 1761 ( 8 )

Abstract:

<P>Background: 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. </P><P> Methods: 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. </P><P> Results: 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. </P><P> Conclusion: 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.</P>

Keywords:

Celastrus orbiculatus, human gastric cancer, metastasis, mTOR, epithelial-mesenchymal transition, PI3K.

Affiliation:

Institute of Traditional Chinese Medicine & Western Medicine, School of Medicine, Yangzhou University, Jiangyang North Road, Yangzhou 225009, Institute of Traditional Chinese Medicine & Western Medicine, School of Medicine, Yangzhou University, Jiangyang North Road, Yangzhou 225009, Institute of Traditional Chinese Medicine & Western Medicine, School of Medicine, Yangzhou University, Jiangyang North Road, Yangzhou 225009, Institute of Traditional Chinese Medicine & Western Medicine, School of Medicine, Yangzhou University, Jiangyang North Road, Yangzhou 225009, Institute of Traditional Chinese Medicine & Western Medicine, School of Medicine, Yangzhou University, Jiangyang North Road, Yangzhou 225009, Institute of Traditional Chinese Medicine & Western Medicine, School of Medicine, Yangzhou University, Jiangyang North Road, Yangzhou 225009, Institute of Traditional Chinese Medicine & Western Medicine, School of Medicine, Yangzhou University, Jiangyang North Road, Yangzhou 225009, Institute of Traditional Chinese Medicine & Western Medicine, School of Medicine, Yangzhou University, Jiangyang North Road, Yangzhou 225009, Institute of Traditional Chinese Medicine & Western Medicine, School of Medicine, Yangzhou University, Jiangyang North Road, Yangzhou 225009, Institute of Traditional Chinese Medicine & Western Medicine, School of Medicine, Yangzhou University, Jiangyang North Road, Yangzhou 225009, Institute of Traditional Chinese Medicine & Western Medicine, School of Medicine, Yangzhou University, Jiangyang North Road, Yangzhou 225009, Department of Pathology, Affiliated Hospital of Yangzhou University, Yangzhou 225001, Institute of Traditional Chinese Medicine & Western Medicine, School of Medicine, Yangzhou University, Jiangyang North Road, Yangzhou 225009, Institute of Traditional Chinese Medicine & Western Medicine, School of Medicine, Yangzhou University, Jiangyang North Road, Yangzhou 225009, Department of Pathology, Affiliated Hospital of Yangzhou University, Yangzhou 225001, Institute of Traditional Chinese Medicine & Western Medicine, School of Medicine, Yangzhou University, Jiangyang North Road, Yangzhou 225009

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