Su Chao, Gong Fengying, You Yanyi, Jiang Ziqing, Wen Xiaohui, Wang Yaran, Lin Sijie, Li Fei, Li Jingjun, Liu Ying, Zhu Daoqi, Fan Qin
The School of Traditional Chinese Medicine, Southern Medical University, No.1023-1063 Shatai South Road, Guangzhou, Guangdong, 510515, China.
Nanfang Hospital, Southern Medical University, No.1023-1063 Shatai South Road, Guangzhou, Guangdong, 510515, China.
QJM. 2025 Jul 3. doi: 10.1093/qjmed/hcaf147.
Radiotherapy is the preferred treatment for nasopharyngeal carcinoma (NPC). Previous studies by our research team have shown that Shengmai Jianghuang San (SMJHS) inhibits the proliferation and migration of hypoxic NPC cells, thereby enhancing their radiosensitivity.
This study aimed to explore the effects and potential molecular mechanisms of action of SMJHS on NPC cell stemness.
Sprague-Dawley rats were administered SMJHS intragastrically, and blood samples were collected from the abdominal aorta. Serum containing the drug was obtained by low-speed centrifugation. The components of the SMJHS-containing serum were analysed using Ultra-Performance Liquid Chromatography-Quadrupole Time-of-Flight Mass Spectrometry. Cobalt chloride was used to simulate cell hypoxia. Methyl Thiazolyl Tetrazolium, colony formation, and tumour sphere formation assays were conducted to assess cell viability, radiosensitivity, and stemness markers, respectively. Stable knockdown cell lines were established using lentivirus transduction. The interactions between NPC cancer stem cells and the tenascin-C (TNC)/HIF-1α/YAP1 pathway were assessed using western blotting and RT-qPCR. The effect of SMJHS on NPC radioresistance was analysed using subcutaneous tumour xenografts in nude mice.
Our study showed that SMJHS inhibited NPC cell growth in vitro, enhanced NPC radiosensitivity, and reduced NPC cell stemness. Compared with the control group, SMJHS significantly suppressed tumour growth, inhibited the expression of TNC, HIF-1α, YAP1, and CD44, and reduced the growth of xenograft tumours in nude mice. These findings suggest that SMJHS enhances radiosensitivity by suppressing cell stemness through the TNC/HIF-1α/YAP1 pathway.
SMJHS improves NPC radiosensitivity by downregulating NPC cell stemness through inhibition of the TNC/HIF-1α/YAP1 signalling pathway.
放射治疗是鼻咽癌（NPC）的首选治疗方法。我们研究团队之前的研究表明，生脉姜黄散（SMJHS）可抑制缺氧NPC细胞的增殖和迁移，从而提高其放射敏感性。
本研究旨在探讨SMJHS对NPC细胞干性的影响及其潜在的分子作用机制。
对Sprague-Dawley大鼠进行SMJHS灌胃，并从腹主动脉采集血样。通过低速离心获得含药血清。使用超高效液相色谱-四极杆飞行时间质谱法分析含SMJHS血清的成分。用氯化钴模拟细胞缺氧。分别进行甲基噻唑基四氮唑、集落形成和肿瘤球形成试验，以评估细胞活力、放射敏感性和干性标志物。使用慢病毒转导建立稳定的敲低细胞系。采用蛋白质免疫印迹法和RT-qPCR评估NPC癌干细胞与腱生蛋白-C（TNC）/缺氧诱导因子-1α（HIF-1α）/Yes相关蛋白1（YAP1）通路之间的相互作用。利用裸鼠皮下肿瘤异种移植模型分析SMJHS对NPC放射抗性的影响。
我们的研究表明，SMJHS在体外抑制NPC细胞生长，提高NPC放射敏感性，并降低NPC细胞干性。与对照组相比，SMJHS显著抑制肿瘤生长，抑制TNC、HIF-1α、YAP1和CD44的表达，并减少裸鼠异种移植肿瘤的生长。这些发现表明，SMJHS通过TNC/HIF-1α/YAP1通路抑制细胞干性来提高放射敏感性。
SMJHS通过抑制TNC/HIF-1α/YAP1信号通路下调NPC细胞干性，从而提高NPC放射敏感性。
