Irisquinone exerts anti-osteosarcoma activity by regulating the PI3K/AKT signaling pathway.

Irisquinone is an active bioactive constituent isolated from the dried rhizomes of Iris tectorum, a traditional Chinese medicinal herb. Accumulating evidence has confirmed that irisquinone exhibits prominent antitumor activity against a variety of human malignancies. Nevertheless, its biological function and precise molecular mechanisms underlying anti-osteosarcoma effects remain poorly clarified. In the present study, we systematically explored the inhibitory effect of irisquinone on osteosarcoma progression via a combination of in vitro cell experiments and in vivo xenograft model validation. Network pharmacology and molecular docking were applied as preliminary computational strategies to predict potential therapeutic targets and downstream signaling pathways of irisquinone. Bioinformatics analysis indicated that the PI3K/AKT signaling axis is closely implicated in the anti-osteosarcoma action of irisquinone, with AKT1 predicted as a core potential target. Further in vitro functional experiments verified that irisquinone markedly suppressed the proliferation and migration capacity of osteosarcoma cells. Mechanistically, irisquinone restrained the activation of the PI3K/AKT signaling pathway, modulated the expression of apoptosis-related Bcl-2 family proteins (Bax and Bcl-2), and ultimately triggered osteosarcoma cell apoptosis. In addition, the anti-tumor effect and pathway regulatory activity of irisquinone were further validated in vivo. Collectively, our findings demonstrate that irisquinone exerts its anti-osteosarcoma function, at least in part, through suppressing the PI3K/AKT signaling pathway. This work provides reliable experimental support and a theoretical foundation for the preclinical application of irisquinone and the development of novel therapeutic agents against osteosarcoma.