Shengmai Jianghuang San Enhances Radiosensitivity of Hypoxic Nasopharyngeal Carcinoma by Inhibiting Cancer Stemness.

Abstract

Background: 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.

Aim: This study aimed to explore the effects and potential molecular mechanisms of action of SMJHS on NPC cell stemness.

Methods: 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.

Results: 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.

Conclusion: SMJHS improves NPC radiosensitivity by downregulating NPC cell stemness through inhibition of the TNC/HIF-1α/YAP1 signalling pathway.