ONC201通过抑制FAK信号通路增强小细胞肺癌的放射敏感性
ONC201 enhances the radiosensitivity of small-cell lung cancer via inhibition of the FAK signaling pathway.
作者
作者单位
- Department of Oncology, Tongji Hospital of Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, P.R. China.
摘要
中文
小细胞肺癌（SCLC）是一种高度侵袭性的神经内分泌恶性肿瘤，预后差。放疗是SCLC的重要治疗策略，但受到快速复发和治疗耐药性的限制。ONC201是一种口服生物利用度高的imipridone化合物，已在多种恶性肿瘤中显示出临床疗效。本研究探讨了ONC201作为SCLC放射增敏剂的治疗潜力。我们的结果表明，ONC201显著抑制SCLC细胞增殖、迁移和侵袭，同时促进细胞周期阻滞和凋亡。此外，ONC201增强了细胞放射敏感性，增强了放疗诱导的G2/M期阻滞，并促进凋亡。机制上，我们证实ONC201通过抑制黏着斑激酶（FAK）信号增强了放射敏感性。总之，我们的研究结果强调了ONC201作为SCLC治疗的有前景的放射增敏剂的潜力。
English
Small-cell lung cancer (SCLC) is a highly aggressive neuroendocrine malignancy with a poor prognosis. Radiotherapy is an essential treatment strategy for SCLC but is constrained by rapid relapse and therapeutic resistance. ONC201, an orally bioavailable imipridone compound, has demonstrated clinical efficacy against various malignancies. This study explored the therapeutic potential of ONC201 as a radiosensitizer in SCLC. Our results showed that ONC201 significantly suppressed SCLC cell proliferation, migration, and invasion, while promoting cell-cycle arrest and apoptosis. Moreover, ONC201 enhanced cellular radiosensitivity, augmented radiotherapy-induced G2/M phase arrest, and promoted apoptosis. Mechanistically, we confirmed that ONC201 enhanced radiosensitivity by suppressing focal adhesion kinase (FAK) signaling. Overall, our findings underscore the potential of ONC201 as a promising radiosensitizer for SCLC treatment.
分类与指标
- 研究类型
- 基础研究
- 病种
- 肺癌
- JCR 分区
- Q1
- 影响因子
- 4.5
- 新锐分区
- 3区