Osteosarcoma (OS) is one of the most common malignant bone tumors, with an incidence of 4-5 per million among children and teenagers. Panax notoginseng saponins (PNS) a derivatives from Panax notoginseng, are potent drugs that have many biological activities including antitumor effects. However, there have been no reports focused on the effect of PNS on OS development.

Material and methods:
MTT and flow cytometry was used to detect the proliferation and apoptosis of OS cells treated by PNS. The expression of miR-760 was identified by qPCR. Luciferase assay was performed to verify the target of miR-760. Western blot was used to detect the expression of target proteins. In vivo analysis was employed to confirm the antitumor effect of PNS.

We tested the PNS effect on a large numbers of microRNAs (miRs) in OS cells, we found that PNS significantly reduced miR-760. Also, luciferase assay has shown SMAD4 to be the target gene of miR-760 in OS cells. Rescue experiments were carried out to verify the relation between SMAD4 and miR-760. we found that overexpression of miR-760 can reverse the effect of PNS. PNS proven to exerts its effect through miR-760. Moreover, SMAD4 can reverse the effect of miR-760, indicating that miR-760 targets SMAD4 in OS cells.

This study extends our understanding of the effect of PNS in OS cell. we revealed a novel signaling pathway involved in the PNS mode of action, miR-760/SMAD4, this new pathway might be feasible as a target for the treatment of OS.