Caulis Spatholobi extracts inhibit osteosarcoma growth and metastasis through suppression of CXCR4/PI3K/AKT signaling

Abstract

Abstract Background The therapeutic potential of Caulis Spatholobi (CS) extracts against various cancers has been well documented, yet its impact and mechanism in osteosarcoma (OS) remain unexplored. This study aims to elucidate the effects of CS extracts on the growth and metastasis of OS, along with its underlying molecular mechanism. Methods The impact of CS extracts on the proliferative potential of two OS cell lines (Saos-2 and U2OS) was assessed using MTT and colony-formation assays. Additionally, the migratory and invasive capacities of OS cells were investigated through Transwell assays. The modulation of CXCR4 expression by CS extracts was evaluated using qRT-PCR and Western blotting. Furthermore, the influence of CS extracts on the activation of PI3K/Akt signaling was determined through Western blotting. Results CS extracts exhibited a dose- and time-dependent inhibition of proliferation and colony formation in OS cells. Notably, CXCR4 expression was prominently observed in Saos-2 and U2OS, and treatment with CS extracts led to a dose-dependently reduction in CXCR4 levels. Silencing CXCR4 or inhibiting its function diminished the migratory and invasive capacities of OS cells. Conversely, the CS extracts induced suppression of OS cell migration and invasion was counteracted by CXCR4 overexpression. Mechanistically, CS extracts repressed PI3K/AKT signaling in OS cells by downregulating CXCR4 expression. Conclusions CS extracts mitigate the CXCR4/PI3K/AKT signaling-mediated growth and metastasis capacities of OS cells, thus might play an anti-tumor role in OS.