Abstract Tanshinone IIA (Tan IIA) is a member of the major lipophilic components extracted from the root of Salvia miltiorrhiza Bunge. Osteosarcomas are primary malignant tumors of bone. The aim of our study is to explore the role of Tan IIA in osteosarcomas survival, migration, and proliferation. MG63 osteosarcoma cell line was cultured in vitro and treated with different concentrations of Tan IIA. Then, ELISA, immunofluorescence, qPCR, western blots, and pathway analysis were conducted to verify whether Tan II modulated osteosarcoma survival, migration, and proliferation through the AMPK/Nrf2 signaling pathway. Our results indicated that Tan IIA dose-dependently inhibited MG63 osteosarcoma cell survival, migration, and proliferation. Mechanistically, Tan IIA reduced cell viability and inhibited the transcriptions of migratory factors. In addition, the number of proliferative MG63 osteosarcoma cell was also reduced by Tan IIA. Molecular investigations demonstrated that Tan IIA treatment caused a drop in the transcriptions and activities of AMPK and Nrf2. Interestingly, knockdown of AMPK and Nrf2 markedly attenuated MG63 osteosarcoma cell survival, migration, and proliferation. Altogether, our results indicate that Tan IIA could be used as an effective anticancer drug to control osteosarcoma proliferation through affecting its survival, migration, and proliferation.

中文翻译：

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丹参酮 IIA 通过调节 AMPK-Nrf2 信号通路抑制骨肉瘤生长

摘要 丹参酮IIA（Tan IIA）是从丹参根中提取的主要亲脂成分之一。骨肉瘤是骨的原发性恶性肿瘤。我们研究的目的是探索 Tan IIA 在骨肉瘤存活、迁移和增殖中的作用。MG63骨肉瘤细胞系体外培养并用不同浓度的Tan IIA处理。然后，进行 ELISA、免疫荧光、qPCR、蛋白质印迹和通路分析，以验证 Tan II 是否通过 AMPK/Nrf2 信号通路调节骨肉瘤的存活、迁移和增殖。我们的结果表明，Tan IIA 剂量依赖性地抑制 MG63 骨肉瘤细胞的存活、迁移和增殖。从机制上讲，Tan IIA 降低了细胞活力并抑制了迁移因子的转录。此外，Tan IIA 还减少了增殖性 MG63 骨肉瘤细胞的数量。分子研究表明，Tan IIA 处理导致 AMPK 和 Nrf2 的转录和活性下降。有趣的是，AMPK 和 Nrf2 的敲低显着减弱了 MG63 骨肉瘤细胞的存活、迁移和增殖。总之，我们的结果表明，Tan IIA 可以作为一种有效的抗癌药物，通过影响其存活、迁移和增殖来控制骨肉瘤的增殖。和扩散。总之，我们的结果表明，Tan IIA 可以作为一种有效的抗癌药物，通过影响其存活、迁移和增殖来控制骨肉瘤的增殖。和扩散。总之，我们的结果表明，Tan IIA 可以作为一种有效的抗癌药物，通过影响其存活、迁移和增殖来控制骨肉瘤的增殖。