Division of General Surgery, Department of Surgery, E-Da Cancer Hospital, I-Shou University, Kaohsiung 824005, Taiwan.
School of Chinese Medicine for Post Baccalaureate, College of Medicine, I-Shou University, Kaohsiung 84001, Taiwan.
Int J Mol Sci. 2024 Nov 4;25(21):11839. doi: 10.3390/ijms252111839.
Radiotherapy combined with a radiosensitizer represents an important treatment for head and neck squamous cell carcinoma (HNSCC). Only a few chemotherapy agents are currently approved as radiosensitizers for targeted therapy. Oral squamous cell carcinoma is one of the deadliest cancers, with approximately ~500,000 new diagnosed cases and 145,000 deaths worldwide per year. The incidence of new cases continues to increase in developing countries. This study aimed to investigate the effect of and on cell viability in OSCC cells. The HNSCC cell line OML1 and its radiation-resistant clone OML1-R were used. The anticancer effect and the mechanism of action of and in OSCC cells were analyzed by using cell viability assays, Western blot analysis, and Tranwell migration assays. The results showed that concentration-dependently reduced the viability of OML1 and OML1-R (radioresistant) cells by downregulating the levels of AKT/mTOR mediators, such as p110α, p85, pAKT (ser473), p-mTOR (ser2448), and p-S6 Ribosomal (ser235/236). We found that cotreatment of OML1 and OML1R cells with either zVAD-FMK (apoptosis inhibitor), Ferrostatin-1 (Fer-1, a ferroptosis inhibitor), or chloroquine (CQ, an autophagy inhibitor) markedly reduced cell death. These results demonstrate that exhibits anti-proliferation activity and highlight the therapeutic potential of small-molecule inhibitors against PI3K/mTOR signaling for radiosensitization in HNC treatment.
放射治疗联合放射增敏剂是头颈部鳞状细胞癌（HNSCC）的重要治疗方法。目前只有少数化疗药物被批准作为靶向治疗的放射增敏剂。口腔鳞状细胞癌是最致命的癌症之一，全世界每年约有 50 万新诊断病例和 14.5 万例死亡。发展中国家新发病例的发病率继续上升。本研究旨在探讨 和 对口腔鳞状细胞癌细胞活力的影响。使用 HNSCC 细胞系 OML1 及其辐射抗性克隆 OML1-R。通过细胞活力测定、Western blot 分析和 Transwell 迁移测定分析 和 对 OSCC 细胞的抗癌作用和作用机制。结果表明， 通过下调 AKT/mTOR 介质（如 p110α、p85、pAKT（ser473）、p-mTOR（ser2448）和 p-S6 核糖体（ser235/236））的水平，浓度依赖性地降低了 OML1 和 OML1-R（辐射抗性）细胞的活力。我们发现，用 zVAD-FMK（凋亡抑制剂）、Ferrostatin-1（Fer-1，铁死亡抑制剂）或氯喹（CQ，自噬抑制剂）共同处理 OML1 和 OML1R 细胞，显著减少细胞死亡。这些结果表明 表现出抗增殖活性，并强调了小分子抑制剂针对 PI3K/mTOR 信号通路在 HNC 治疗中放射增敏的治疗潜力。
