Osteosarcoma (OS) is the most frequent type of primitive malignant bone tumor with a poor prognosis due to distant metastasis. Our previous studies have demonstrated that IRX2 is overexpressed and is important in cell proliferation and invasion. However, the molecular mechanisms underlying the IRX2‑dependent regulation of OS progression remains to be elucidated. In the present study, the effects of IRX2 on the upregulation of MMP2 and VEGF in OS were determined by western blotting, and the underlying molecular mechanisms were elucidated. These findings provided data suggesting that IRX2 modulates the expression levels of MMP2 and VEGF in an AKT‑dependent manner. The overexpression of IRX2 promoted the activation of PI3K/Akt and increased the proliferation and invasiveness of the OS cell lines as shown by CCK8 and invasion assays. Notably, interruption of the AKT pathway by treatment with LY294002, a specific PI3K inhibitor, attenuated IRX2‑induced cell proliferation and invasive ability, and the upregulation of MMP2 and VEGF. The results of the present study suggested that inhibition of the IRX2‑mediated AKT signaling pathway may be a suitable therapeutic target for the treatment of OS.

中文翻译：

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IRX2以PI3K / AKT依赖性方式介导MMP-9和VEGF的上调。

骨肉瘤（OS）是最常见的原发性恶性骨肿瘤，由于远处转移而预后较差。我们以前的研究表明，IRX2是过表达的，在细胞增殖和侵袭中很重要。但是，IRX2依赖的OS进程调节的分子机制仍有待阐明。在本研究中，通过蛋白质印迹法确定了IRX2对OS中MMP2和VEGF上调的作用，并阐明了其潜在的分子机制。这些发现提供的数据表明，IRX2以AKT依赖性方式调节MMP2和VEGF的表达水平。ICK2的过表达促进了PI3K / Akt的激活，并增加了OS细胞系的增殖和侵袭性，如CCK8和侵袭试验所示。尤其，通过使用特定PI3K抑制剂LY294002的治疗来中断AKT途径，减弱IRX2诱导的细胞增殖和侵袭能力，并上调MMP2和VEGF。本研究的结果表明，抑制IRX2介导的AKT信号通路可能是治疗OS的合适治疗靶标。