In:
Anti-Cancer Agents in Medicinal Chemistry, Bentham Science Publishers Ltd., Vol. 19, No. 14 ( 2019-12-16), p. 1754-1761
Kurzfassung:
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. 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. 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. 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.
Materialart:
Online-Ressource
ISSN:
1871-5206
DOI:
10.2174/1871520619666190731162722
Sprache:
Englisch
Verlag:
Bentham Science Publishers Ltd.
Publikationsdatum:
2019
SSG:
15,3
