The Fifth Affiliated Hospital of Guangxi Medical University, Nanning, China.
Graduate School of Guangxi Medical University, Nanning, China.
Biomed Pharmacother. 2022 Jun;150:113012. doi: 10.1016/j.biopha.2022.113012. Epub 2022 Apr 28.
Nasopharyngeal carcinoma (NPC) is a malignant tumor highly prevalent in Southeast Asia. The distant metastasis and disease recurrence are still unsolved clinical problems. In recent years, traditional Chinese medicine (TCM) monomers have become significantly attractive due to their advantages. Using high throughput drug sensitivity screening, we identified gambogic acid (GA) as a common TCM monomer displaying multiple anti-NPC effects. GA could effectively inhibit the proliferation of low differentiated cells and highly metastatic cells in NPC via inducing apoptosis and G2/M cell cycle arrest. In addition, GA obviously repressed the abilities of cell clone, migration, invasion, angiogenesis and represented satisfied synergistic effects combined with chemotherapy. Importantly, we found the elevated immune checkpoint CD47 stimulated after chemotherapy was dramatically impaired by GA treatment. Mechanically, the network pharmacology analyses unraveled that the oncogenic signaling pathways including STATs were rewired by GA treatment. Taken together, our study reveals a molecular basis and provides a rationale for GA application as the treatment regime in NPC therapy in future.
鼻咽癌（NPC）是一种在东南亚地区高发的恶性肿瘤。远处转移和疾病复发仍然是尚未解决的临床问题。近年来，由于其优势，中药单体已成为研究热点。通过高通量药物敏感筛选，我们发现藤黄酸（GA）是一种具有多种抗 NPC 作用的常见中药单体。GA 可通过诱导细胞凋亡和 G2/M 细胞周期阻滞，有效抑制 NPC 中低分化细胞和高转移细胞的增殖。此外，GA 明显抑制细胞克隆、迁移、侵袭和血管生成的能力，并与化疗表现出令人满意的协同作用。重要的是，我们发现化疗后升高的免疫检查点 CD47 被 GA 处理显著破坏。从机制上讲，网络药理学分析表明，GA 处理重排了包括 STATs 在内的致癌信号通路。综上所述，我们的研究揭示了一个分子基础，并为 GA 在未来 NPC 治疗中的应用提供了一个合理的方案。
