Abstract:
Shengmai Jianghuang San (SMJHS) is a traditional Chinese herbal compound reported to inhibit Nasopharyngeal Carcinoma (NPC) progression and enhance radiosensitivity. However, the specific active ingredients and regulatory mechanisms of SMJHS against NPC, particularly under hypoxic conditions, remain unclear. In this study, Sprague-Dawley (SD) rats were gavaged with Shengmai Jianghuang San (SMJHS), and their blood was collected from the abdominal aorta. UHPLC-Q-Exactive orbitrap MS/MS was used to identify the metabolite profiles of SMJHS drug-containing serum. A molecular network of the active compositions in SMJHS targeting NPC was constructed through network pharmacology and molecular docking. The HIF-1α/VEGF pathway was in key positions. The effects of SMJHS on the proliferation, migration, and radiosensitivity of hypoxic NPC cells were assessed by in vitro experiments. NPC cell lines stably overexpressing HIF-1α were established using a lentivirus to investigate the regulation of HIF-1α/VEGF signaling in hypoxic NPC cells by SMJHS. Through a combination of network pharmacological analysis, cellular biofunctional validation, and molecular biochemical experiments, our study found that SMJHS had an anti-proliferative effect on NPC cells cultured under hypoxic conditions, inhibiting their migration and increasing their radiosensitivity. Additionally, SMJHS suppressed the expression of HIF-1α and VEGFA, exhibiting potential as an effective option for improving NPC treatment.
摘要:
生脉健黄散(SMJHS)是一种传统的中药复方,据报道可以抑制鼻咽癌(NPC)的进展并增强放射敏感性。然而,SMJHS抗鼻咽癌的具体活性成分和调控机制,特别是在缺氧条件下,仍然不清楚。在这项研究中,Sprague-Dawley(SD)大鼠用生脉健黄散(SMJHS)灌胃,他们的血液是从腹主动脉采集的.UHPLC-Q-ExactiveorbitrapMS/MS用于鉴定SMJHS含药血清的代谢物谱。通过网络药理学和分子对接,构建了SMJHS靶向NPC中活性成分的分子网络。HIF-1α/VEGF通路处于关键位置。SMJHS对细胞增殖的影响,迁移,通过体外实验评估缺氧NPC细胞的放射敏感性。使用慢病毒建立稳定过表达HIF-1α的NPC细胞系,以研究SMJHS对缺氧NPC细胞中HIF-1α/VEGF信号传导的调节。通过结合网络药理分析,细胞生物功能验证,分子生化实验,我们的研究发现SMJHS对缺氧条件下培养的NPC细胞具有抗增殖作用,抑制其迁移并增加其放射敏感性。此外,SMJHS抑制HIF-1α和VEGFA的表达,显示作为改善NPC治疗的有效选择的潜力。