Department of Oral and Maxillofacial Surgery, The First Affiliated Hospital of Harbin Medical University, Harbin, 150001, China.
Sichuan Engineering Research Center for Biomimetic Synthesis of Natural Drugs, School of Life Science and Engineering, Southwest Jiaotong University, Chengdu, 610031, China.
Biochem Biophys Res Commun. 2024 May 21;709:149842. doi: 10.1016/j.bbrc.2024.149842. Epub 2024 Mar 27.
Oral squamous cell carcinoma (OSCC), a malignancy originating from mucosal epithelial cells. Currently, triggering apoptotic cell death with anticancer drugs is the main way to inhibit OSCC cells. However, the capability to trigger apoptosis in tumors is constrained by the intrinsic resistance of tumor cells to apoptosis, hampering its effectiveness. Thus, utilizing alternative modes of non-apoptotic cell death offers new therapeutic possibilities, such as using a drug combination strategy to simultaneously induce ferroptosis and autophagy has the potential to improve OSCC therapy. In this study, we found the ferroptosis inducer RSL3 has certain inhibitory effects on the proliferation and migration of OSCC cells. Interestingly, our studies showed that RSL3 is also associated with autophagy activation. Based on this finding, we tried to combine RSL3 with the autophagy inducer LYN-1604 to improve the therapeutic effect. The results demonstrated that simultaneous regulation of autophagy and ferroptosis significantly reduced the proliferation and migration of OSCC cells. Taken together, we demonstrated the therapeutic potential of RSL3 in OSCC cells and proposed that simultaneous activation of autophagy and ferroptosis have synergistic effects, which would provide valuable clues for further exploration of targeted therapy for OSCC.
口腔鳞状细胞癌 (OSCC) 是一种起源于黏膜上皮细胞的恶性肿瘤。目前，使用抗癌药物触发细胞凋亡是抑制 OSCC 细胞的主要方法。然而，肿瘤细胞内在的抗凋亡能力限制了其触发凋亡的能力，从而影响了其疗效。因此，利用非凋亡细胞死亡的替代模式提供了新的治疗可能性，例如使用药物联合策略同时诱导铁死亡和自噬，有可能改善 OSCC 的治疗效果。在本研究中，我们发现铁死亡诱导剂 RSL3 对 OSCC 细胞的增殖和迁移具有一定的抑制作用。有趣的是，我们的研究表明，RSL3 还与自噬激活有关。基于这一发现，我们试图将 RSL3 与自噬诱导剂 LYN-1604 联合使用以提高治疗效果。结果表明，自噬和铁死亡的同时调控显著降低了 OSCC 细胞的增殖和迁移。综上所述，我们证明了 RSL3 在 OSCC 细胞中的治疗潜力，并提出自噬和铁死亡的同时激活具有协同作用，这将为进一步探索 OSCC 的靶向治疗提供有价值的线索。
