Ginsenoside Rb1 suppresses the proliferation and tumorigenesis of U2OS osteosarcoma cells via downregulating PI3K/Akt signaling

Abstract

As the most prevalent malignant bone tumor, osteosarcoma (OS) primarily affects children and adolescents. Current treatment options for OS are limited by early metastasis, chemotherapy resistance, and severe side effects. Ginsenoside Rb1, a natural compound derived from Panax ginseng, has demonstrated anticancer effects on various tumor types, but its effects on OS remained to be unexplored. We examined the antitumor effect of Ginsenoside Rb1 on U2OS OS cells by cytotoxicity assay, scratch-wound healing assay, transwell assay, etc., and elucidated its underlying molecular mechanisms. Ginsenoside Rb1 significantly inhibited U2OS cell proliferation, migration, and invasion depending on the dosage while simultaneously inducing early apoptosis. Mechanistically, Ginsenoside Rb1 suppressed the PI3K/Akt signaling pathway, reducing Akt phosphorylation and downstream targets including MMP-9 and MMP-2 and cyclin D1. Ginsenoside Rb1 modulated proteins associated with apoptosis, upregulating the level of caspase-3, caspase-8, and Bax and downregulating that of Bcl-2. Ginsenoside Rb1 exerted its antitumor effects through inhibiting the PI3K/Akt signaling pathway and its downstream mediators, thereby suppressing the proliferative and metastatic behaviors of U2OS cells while promoting apoptosis. This study highlighted the potential of Ginsenoside Rb1 as a novel treatment agent against OS. However, further in vivo studies are required to assess its clinical applicability.