Tong Guoxiang, Peng Tianhao, Chen Ya, Sha Lijuan, Dai Huikang, Xiang Yidong, Zou Zhiqi, He Heli, Wang Sha
Academician Workstation, Changsha Medical University, Changsha, China.
Department of Endocrinology, The First Affiliated Hospital of Changsha Medical University, Changsha, China.
Front Pharmacol. 2022 Aug 10;13:901559. doi: 10.3389/fphar.2022.901559. eCollection 2022.
Colorectal cancer (CRC) has become one of the top ten malignant tumors with a high incidence rate and mortality. Due to the lack of a good CRC screening program, most of the CRC patients are being transferred at the time of treatment. The conventional treatment cannot effectively improve the prognosis of CRC patients, and the target drugs can significantly prolong the overall survival of patients in the advanced stage. However, the use of single drug may lead to acquired drug resistance and various serious complications. Therefore, combined targeted drug therapy is the main alternative treatment with poor effect of single targeted drug therapy, which has important research significance for the treatment of CRC. Therefore, this study intends to culture CRC cell lines at the cell level and intervene with the GLP-1 receptor agonist liraglutide. The effects of liraglutide on the PI3K/Akt/mTOR signal pathway and CRC cell proliferation, cycle, migration, invasion, and apoptosis are explored by detecting cell proliferation, cycle, migration, invasion, and apoptosis and the expression of related mRNA and protein. The results showed that liraglutide, a GLP-1 receptor agonist, could block the CRC cell cycle, reduce cell proliferation, migration, and invasion and promote apoptosis by inhibiting the PI3K/Akt/mTOR signal pathway.
结直肠癌(CRC)已成为发病率和死亡率较高的十大恶性肿瘤之一。由于缺乏良好的CRC筛查项目,大多数CRC患者在治疗时已处于转移状态。传统治疗方法无法有效改善CRC患者的预后,而靶向药物可显著延长晚期患者的总生存期。然而,使用单一药物可能会导致获得性耐药和各种严重并发症。因此,联合靶向药物治疗是单一靶向药物治疗效果不佳时的主要替代治疗方法,对CRC的治疗具有重要的研究意义。因此,本研究旨在在细胞水平培养CRC细胞系,并用胰高血糖素样肽-1(GLP-1)受体激动剂利拉鲁肽进行干预。通过检测细胞增殖、周期、迁移、侵袭和凋亡以及相关mRNA和蛋白的表达,探讨利拉鲁肽对PI3K/Akt/mTOR信号通路及CRC细胞增殖、周期、迁移、侵袭和凋亡的影响。结果表明,GLP-1受体激动剂利拉鲁肽可通过抑制PI3K/Akt/mTOR信号通路来阻断CRC细胞周期,减少细胞增殖、迁移和侵袭,并促进细胞凋亡。