Abstract
Salidroside is an active ingredient extracted from Rhodiola rosea that has anti-tumor activities. The current paper attempted to assess the impact of Salidroside on gastric cancer (GC) and explore the potential mechanism. GC cell lines (SNU-216 and MGC803) and gastric epithelial cell line GES-1 were treated with Salidroside. CCK-8 assay, colony formation assay, flow cytometry and Transwell assay were respectively performed to evaluate GC cells phenotype. qRT-PCR and western blot were conducted to reveal the downstream genes and signaling of Salidroside. We found that 800 μM Salidroside was capable of reducing GC cells viability, while has no such impacts on GES-1 cells. Salidroside inhibited GC cells proliferation, migration, invasion and promoted apoptosis, which coupled with the down-regulation of p21, Bcl-2, MMP2, RhoA, p-ROCK1, Vimentin and the up-regulations of CyclinD1, Bax, cleaved caspases. miR-99a was found to be highly expressed in response to Salidroside treatment. Besides, the inhibition of MAPK/ERK and PI3K/AKT signaling induced by Salidroside was attenuated by miR-99a silence and in this process, IGF1R worked as a target of miR-99a. The anti-GC effect of Salidroside was also confirmed in a mouse model of GC. The promoting effect of Salidroside on miR-99a expression was also verified in vivo. Furthermore, Salidroside promoted the cisplatin-sensitivity of SGC7901/DDP cells. In conclusion, this study demonstrated that Salidroside possessed anti-GC effects through regulating miR-99a/IGF1R axis and inhibiting MAPK/ERK and PI3K/AKT pathways.