Department of Traumatology and Orthopaedics, Affiliated Hospital of Chengde Medical University, Chengde 067000, Hebei, China.
Department of General Surgery, Beijing Shijitan Hospital, Capital Medical University, Beijing 100038, China.
Aging (Albany NY). 2023 Jun 10;15(11):5125-5143. doi: 10.18632/aging.204786.
To explore the antitumor effects of angelicin on osteosarcoma and the underlying mechanism. We aimed to elucidate the mechanism by network pharmacology, molecular docking, and experiments. We analyzed a PPI network of potential angelicin targets in the treatment of osteosarcoma and identified hub targets. We systematically performed GO and KEGG enrichment analyses of the potential targets of angelicin, and we predicted it function in osteosarcoma treatment and the underlying molecular mechanism. Through molecular docking, the interactions between hub targets and angelicin were simulated, and then, the hub targets of angelicin were identified. Based on these results, we validated the effects of angelicin on osteosarcoma cells by conducting experiments. The PPI network analysis of potential therapeutic targets identified four apoptosis-related hub targets, namely, BCL-2, Casp9, BAX and BIRC 2. GO and KEGG enrichment analyses demonstrated that angelicin regulates osteosarcoma cell apoptosis. Molecular docking results indicated that angelicin can freely bind to the hub targets listed above. experiments showed that angelicin promoted osteosarcoma cell apoptosis in a dose-dependent manner and inhibited osteosarcoma cell migration and proliferation in a time- and dose-dependent manner. The RT-PCR results showed that angelicin simultaneously promoted the mRNA expression of Bcl-2 and Casp9 and inhibited the mRNA expression of BAX and BIRC 2. Angelicin promotes osteosarcoma cell apoptosis and inhibits osteosarcoma cell proliferation and migration by activating a signaling network that is composed of hub targets that link multiple signaling pathways. Angelicin could become an alternative drug for the treatment of osteosarcoma.
探讨花椒毒素治疗骨肉瘤的抗肿瘤作用及其作用机制。我们旨在通过网络药理学、分子对接和实验来阐明其作用机制。我们分析了花椒毒素治疗骨肉瘤的潜在靶点的 PPI 网络，并确定了枢纽靶点。我们系统地对花椒毒素潜在靶点进行了 GO 和 KEGG 富集分析，预测了其在骨肉瘤治疗中的功能和潜在的分子机制。通过分子对接模拟了枢纽靶点与花椒毒素的相互作用，然后确定了花椒毒素的枢纽靶点。基于这些结果，我们通过实验验证了花椒毒素对骨肉瘤细胞的作用。潜在治疗靶点的 PPI 网络分析确定了四个与细胞凋亡相关的枢纽靶点，即 BCL-2、Casp9、BAX 和 BIRC2。GO 和 KEGG 富集分析表明花椒毒素调节骨肉瘤细胞凋亡。分子对接结果表明花椒毒素可以自由结合到上述枢纽靶点上。实验表明，花椒毒素呈剂量依赖性地促进骨肉瘤细胞凋亡，并呈时间和剂量依赖性地抑制骨肉瘤细胞迁移和增殖。RT-PCR 结果表明，花椒毒素同时促进了 Bcl-2 和 Casp9 的 mRNA 表达，抑制了 BAX 和 BIRC2 的 mRNA 表达。花椒毒素通过激活一个由多个信号通路连接的枢纽靶点组成的信号网络，促进骨肉瘤细胞凋亡，抑制骨肉瘤细胞增殖和迁移。花椒毒素可能成为治疗骨肉瘤的一种替代药物。
