College of Life Sciences, Wuhan University, Wuhan 430072, China.
Department of Gynecology, Maternal and Child Health Hospital of Hubei Province, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430070, China.
Biochem Pharmacol. 2023 Nov;217:115834. doi: 10.1016/j.bcp.2023.115834. Epub 2023 Sep 29.
The emergence of chemoresistance in cervical cancer is extremely challenging in chemotherapy. Oxidative stress has emerged as the regulatory factor in drug resistance, but the detailed mechanism is still unknown. Stress granules, are membrane-less ribonucleoprotein-based condensates, could enhance chemoresistance by sequestering proapoptotic proteins inhibition of cell death upon exposure to drug-induced oxidative stress. Galectin-7, a member of galectin family, exerts varied roles in tumor repression or progression in different cancers. However, its role in cervical cancer has not been sufficiently studied. Here, we found that galectin-7 promotes cisplatin (CDDP) induced apoptosis and associates with stress granule-nucleating protein G3BP1 degradation. With the treatment of cisplatin, galectin-7 could enhance apoptosis by upregulating cleaved-PARP1 and the generation of reactive oxygen species (ROS), promoting mitochondrial fission, and reducing mitochondrial membrane potential (MMP). Furthermore, galectin-7 also reduces resistance by facilitating cisplatin-induced stress granules clearance through galectin-7/RACK1/G3BP1 axis. All these data suggested that galectin-7 promotes cisplatin sensitivity, and it would be potential target for potentiating efficacy in cervical cancer chemotherapy.
宫颈癌化疗耐药的出现极具挑战性。氧化应激已成为耐药性的调节因子，但详细机制尚不清楚。应激颗粒是无膜的核糖核蛋白基凝聚物，可通过隔离促凋亡蛋白来增强耐药性，从而抑制细胞在药物诱导的氧化应激下死亡。半乳糖凝集素-7 是半乳糖凝集素家族的一员，在不同癌症中对肿瘤抑制或进展发挥着不同的作用。然而，其在宫颈癌中的作用尚未得到充分研究。在这里，我们发现半乳糖凝集素-7 可促进顺铂（CDDP）诱导的细胞凋亡，并与应激颗粒成核蛋白 G3BP1 的降解有关。用顺铂处理后，半乳糖凝集素-7 通过上调裂解的 PARP1 和活性氧（ROS）的产生、促进线粒体裂变和降低线粒体膜电位（MMP）来增强凋亡。此外，半乳糖凝集素-7 还通过半乳糖凝集素-7/RACK1/G3BP1 轴促进顺铂诱导的应激颗粒清除来降低耐药性。所有这些数据表明，半乳糖凝集素-7 可增强顺铂敏感性，有望成为增强宫颈癌化疗疗效的潜在靶点。
