Add time:08/23/2019         Source:sciencedirect.com

Ginsenoside Rg3, isolated from the roots of Panax ginseng, has been found to exert anti-cancer activity on multiple human cancers. However, there is no any literature available about the effect of Rg3 on oral squamous cell carcinoma (OSCC). This study investigated the possible anti-cancer effects of Rg3 on OSCC, as well as the possible molecular mechanisms. In vitro, cell viability and proliferation were respectively detected by CCK-8 assay and BrdU assay. Cell apoptosis was detected by Annexin V-FITC/PI assay. Cell transfection was used to change the expression of miR-221 and TIMP3. qRT-PCR and western blotting were performed to measure the expression of molecules involving in cell apoptosis, epithelial-mesenchymal transition (EMT) process, PI3K/AKT pathway and MAPK/ERK pathway. In vivo, OSCC orthotopic murine model was established and tumor volumes were measured. We found that Rg3 treatment inhibited viability, proliferation and EMT process of human OSCC SCC-9 and HSC-5 cells, but promoted cell apoptosis. miR-221 was highly expressed in OSCC tissues and cells. Rg3 reduced the expression of miR-221 in OSCC cells. Up-regulation of miR-221 abrogated the effects of Rg3 on SCC-9 and HSC-5 cell viability, proliferation, apoptosis and EMT process. TIMP3 was lowly expressed in OSCC tissues and cells, which was a direct target gene of miR-221. Rg3 inactivated PI3K/AKT and MAPK/ERK pathways in SCC-9 cells by up-regulating TIMP3. In vivo, Rg3 reduced the tumor volume of OSCC orthotopic murine model. In conclusion, Rg3 exerted anti-cancer effects on OSCC might be via down-regulating miR-221, up-regulating TIMP3, and then inactivating PI3K/AKT and MAPK/ERK pathways.

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