CUDC-907 inhibits osteosarcoma through upregulation of PTX3 and inhibition of PI3K-AKT signaling.
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Osteosarcoma is the most common primary malignant bone tumor in adolescents, causing severe socioeconomic burden on society. CUDC-907 is a newly developed drug by directly inhibiting PI3K and exerts effects on many tumors. It has also been reported that CUDC-907 inhibits the stemness of neuroblastoma by targeting on pentraxin 3 (PTX3), which, as an innate immune molecule, is widely involved in a wide range of physiological and pathological activities of the organism and in the development of a variety of tumors, but its role in osteosarcoma has not been investigated. CUDC-907 was co-cultured with the osteosarcoma cell lines U2OS and HOS to detect their effects on cellular phenotype. PTX3-knockdown osteosarcoma cell lines were constructed to test the role of PTX3 in tumor phenotype. Xenograft model in nude mice were performed to further validate the role of PTX3. RNA sequencing was used to detect the relevant signaling pathways. As a results, CUDC-907 has been demonstrated to play significant inhibitory roles on osteosarcoma cells. Meanwhile, this study found that PTX3 showed low expression in osteosarcoma, and CUDC-907 could increase the expression of PTX3. This study further demonstrated that CUDC-907 related endogenous upregulation of PTX3 promotes apoptosis of osteosarcoma cells by inhibiting the PI3K-AKT pathway, which in turn elucidated the potential mechanism of osteosarcoma inhibition by CUDC-907. In conclusion, CUDC-907 promote apoptosis in osteosarcoma cells by promoting PTX3 expression and thus inhibiting the PI3K-AKT pathway.