■头颈部鳞状细胞癌(HNSCC)在全球范围内普遍存在,复发率高,存活率低,以及患者生活质量差。来自PAC-1的SM-1可以激活proaspase-3并诱导癌细胞凋亡以发挥抗肿瘤作用。然而,联合放疗后SM-1对HNSCC的抑制作用尚不清楚。本研究旨在探讨SM-1对HNSCC的体内外放射增敏作用。
■MTT方法用于检测SM-1对HNSCC细胞系(HONE1,HSC-2和CAL27)活力的影响。通过集落形成实验确定SM-1联合辐射对HONE1,HSC-2和CAL27细胞系存活指数的影响。采用流式细胞术观察SM-1与放疗联合应用对细胞凋亡和细胞周期的影响,进行蛋白质印迹实验以检测细胞凋亡和细胞周期相关蛋白的表达。最后,建立CAL27异种移植瘤模型,评价SM-1联合放射的体内抗肿瘤作用。
■体外,SM-1有效抑制HNSCC细胞系HONE1、HSC-2和CAL27细胞的活性,并在联合照射过程中协同表现出抗增殖活性。同时,SM-1对HNSCC的抗肿瘤作用高于Debio1143,细胞的放射敏感性大大提高。流式细胞术和westernblot分析表明,SM-1通过抑制CyclinB1和CDC2的表达,诱导头颈部鳞状细胞癌细胞G2/M期阻滞。此外,SM-1激活caspase-3活性并上调PARP1的裂解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在体外和体内增强了HNSCC细胞的辐射敏感性,支持其作为放射增敏剂的潜力与放射治疗相结合的临床试验。
UNASSIGNED: 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.
UNASSIGNED: 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.
UNASSIGNED: 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.
UNASSIGNED: 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.