Department of Pharmacology and Medicinal Chemistry, Jiangsu Vocational College of Medicine, Yancheng, 224005, Jiangsu, People's Republic of China.
Clinical Pharmacology Laboratory, Jiangsu Provincial Hospital of Traditional Chinese Medicine, Nanjing, 210004, Jiangsu, People's Republic of China.
Med Oncol. 2024 Jun 7;41(7):170. doi: 10.1007/s12032-024-02413-6.
Salvianolic acid B (Sal B) has demonstrated anticancer activity against various types of cancer. However, the underlying mechanism of Sal B-mediated anticancer effects remains incompletely understood. This study aims to investigate the impact of Sal B on the growth and metastasis of human A549 lung cells, as well as elucidate its potential mechanisms. In this study, different concentrations of Sal B were administered to A549 cells. The effects on migration and invasion abilities were assessed using MTT, wound healing, and transwell assays. Flow cytometry analysis was employed to evaluate Sal B-induced apoptosis in A549 cells. Western blotting and immunohistochemistry were conducted to measure the expression levels of cleaved caspase-3, cleaved PARP, and E-cadherin. Commercial kits were utilized for detecting intracellular reactive oxygen species (ROS) and NAD. Additionally, a xenograft model with transplanted A549 tumors was employed to assess the anti-tumor effect of Sal B in vivo. The expression levels of NDRG2, p-PTEN, and p-AKT were determined through western blotting. Our findings demonstrate that Sal B effectively inhibits proliferation, migration, and invasion in A549 cells while inducing dose-dependent apoptosis. These apoptotic responses and inhibition of tumor cell metastasis are accompanied by alterations in intracellular ROS levels and NAD/NADH ratio. Furthermore, our in vivo experiment reveals that Sal B significantly suppresses A549 tumor growth compared to an untreated control group while promoting increased cleavage of caspase-3 and PARP. Importantly, we observe that Sal B upregulates NDRG2 expression while downregulating p-PTEN and p-AKT expressions. Collectively, our results provide compelling evidence supporting the ability of Sal B to inhibit both growth and metastasis in A549 lung cancer cells through oxidative stress modulation as well as involvement of the NDRG2/PTEN/AKT pathway.
丹酚酸 B（Sal B）已被证明对多种类型的癌症具有抗癌活性。然而，Sal B 介导的抗癌作用的潜在机制仍不完全清楚。本研究旨在探讨 Sal B 对人 A549 肺细胞生长和转移的影响，并阐明其潜在机制。在这项研究中，向 A549 细胞中给予不同浓度的 Sal B。使用 MTT、划痕愈合和 Transwell 测定评估对迁移和侵袭能力的影响。流式细胞术分析用于评估 Sal B 诱导的 A549 细胞凋亡。Western blot 和免疫组化用于测量 cleaved caspase-3、cleaved PARP 和 E-cadherin 的表达水平。使用商业试剂盒检测细胞内活性氧（ROS）和 NAD。此外，还使用移植了 A549 肿瘤的异种移植模型来评估 Sal B 在体内的抗肿瘤作用。通过 Western blot 确定 NDRG2、p-PTEN 和 p-AKT 的表达水平。我们的研究结果表明，Sal B 可有效抑制 A549 细胞的增殖、迁移和侵袭，同时诱导剂量依赖性凋亡。这些凋亡反应和肿瘤细胞转移的抑制伴随着细胞内 ROS 水平和 NAD/NADH 比的改变。此外，我们的体内实验表明，与未处理的对照组相比，Sal B 显著抑制 A549 肿瘤的生长，同时促进 caspase-3 和 PARP 的裂解增加。重要的是，我们观察到 Sal B 上调 NDRG2 的表达，同时下调 p-PTEN 和 p-AKT 的表达。总之，我们的研究结果提供了令人信服的证据，表明 Sal B 通过氧化应激调节以及涉及 NDRG2/PTEN/AKT 途径来抑制 A549 肺癌细胞的生长和转移。
