头颈鳞状细胞癌（HNSCC）在全球范围内普遍存在，其复发率高、生存率低、患者生活质量差。 SM-1源自PAC-1，可以激活procaspase-3并诱导癌细胞凋亡，从而发挥抗肿瘤作用。然而，SM-1联合放射治疗后对HNSCC的抑制作用尚不清楚。本研究旨在探讨SM-1在体外和体内对HNSCC的放射增敏作用。采用MTT法检测SM-1对HNSCC细胞系（HONE1、HSC-2和CAL27）活力的影响。通过集落形成实验测定SM-1联合辐射对HONE1、HSC-2和CAL27细胞系存活指数的影响。采用流式细胞术研究SM-1和放射组合对细胞凋亡和细胞周期的影响，并进行Western blot实验检测细胞凋亡和细胞周期相关蛋白的表达。最后建立CAL27异种移植肿瘤模型，评价SM-1联合放射线体内抗肿瘤作用。在体外，SM-1有效抑制HNSCC细胞系HONE1、HSC-2和CAL27细胞的活性，并在联合照射期间协同显示抗增殖活性。同时，SM-1对HNSCC的抗肿瘤作用高于Debio1143，并且细胞的放射敏感性大大增加。流式细胞术和蛋白质印迹分析表明，SM-1通过抑制CyclinB1和CDC2的表达，诱导头颈部鳞癌细胞G2/M期阻滞。此外，SM-1激活caspase-3活性并上调PARP1的切割形式以诱导细胞凋亡。在体内，SM-1联合照射显示出良好的抗肿瘤效果。SM-1在体外和体内增强HNSCC细胞的放射敏感性，支持其作为放射增敏剂与放疗联合进行临床试验的潜力。

Head and neck squamous cell carcinoma (HNSCC) is globally prevalent with high recurrence, low survival rate, and poor quality of life for patients. Derived from PAC-1, SM-1 can activate procaspase-3 and induce apoptosis in cancer cells to exert anti-tumor effects. However, the inhibitory effect of SM-1 on HNSCC after combination with radiation are unclear. This study aims to investigate the radiosensitizing effect of SM-1 on HNSCC in vitro and in vivo.MTT method was used to detect the effect of SM-1 on the viability of HNSCC cell lines (HONE1, HSC-2, and CAL27). The effects of SM-1 combined with radiation on the survival index of HONE1, HSC-2, and CAL27 cell lines were determined by colony formation assay. Flow cytometry was used to investigate the effects of SM-1 and radiation combination on cell apoptosis and cell cycle, and western blot experiments were performed to detect the expression of apoptosis and cell cycle-related proteins. Finally, a xenograft tumor model of CAL27 was established to evaluate the anti-tumor effect of SM-1 combined with radiation in vivo.In vitro, SM-1 effectively inhibited the activity of HNSCC cell lines HONE1, HSC-2, and CAL27 cells, and synergistically showed anti-proliferation activity during combined irradiation. Meanwhile, anti-tumor effect of SM-1 on HNSCC was higher than that of Debio1143, and the radiosensitivity of cells was greatly increased. Flow cytometry and western blot analysis showed that SM-1 induced G2/M phase arrest of head and neck squamous cell carcinoma cells via inhibiting the expression of CyclinB1 and CDC2. Moreover, SM-1 activated caspase-3 activity and up-regulated the cleaved form of PARP1 to induce cell apoptosis. In vivo, SM-1 combined irradiation showed a good anti-tumor effect.SM-1 enhances HNSCC cell radiation sensitivity in vitro and in vivo, supporting its potential as a radiosensitizer for clinical trials in combination with radiotherapy.