Department of Chemistry, Zhongshan Hospital, and Obstetrics and Gynecology Hospital, Fudan University, Shanghai, 200000, China.
Department of Chemistry, Zhongshan Hospital, and Obstetrics and Gynecology Hospital, Fudan University, Shanghai, 200000, China.
Talanta. 2025 Jan 1;281:126839. doi: 10.1016/j.talanta.2024.126839. Epub 2024 Sep 10.
Cervical cancer remains a significant global health issue due to its high morbidity and mortality rates. Recently, Lactobacillus crispatus has been recognized for its crucial role in maintaining cervical health. While some studies have explored the use of L. crispatus to mitigate cervical cancer, the underlying mechanisms remain largely unknown. In this study, we employed non-targeted proteomics and metabolomics to investigate how L. crispatus affects the growth of cervical cancer cells (SiHa) and normal cervical cells (Ect1/E6E7). Our findings indicated that the inhibitory effect of L. crispatus on SiHa cells was associated with various biological processes, notably the ferroptosis pathway. Specifically, L. crispatus was found to regulate the expression of proteins such as HMOX1, SLC39A14, VDAC2, ACSL4, and LPCAT3 by SiHa cells, which are closely related to ferroptosis. Additionally, it activated the tricarboxylic acid (TCA) cycle in SiHa cells, leading to increased levels of reactive oxygen species (ROS) and lipid peroxides (LPO). These results revealed the therapeutic potential of L. crispatus in targeting the ferroptosis pathway for cervical cancer treatment, opening new avenues for research and therapy in cervical cancer.
宫颈癌仍然是一个重大的全球健康问题，因为它的高发病率和死亡率。最近，已经认识到脆拟杆菌在维持宫颈健康方面的关键作用。虽然一些研究已经探索了使用脆拟杆菌来减轻宫颈癌，但潜在的机制在很大程度上仍然未知。在这项研究中，我们采用非靶向蛋白质组学和代谢组学来研究脆拟杆菌如何影响宫颈癌细胞（SiHa）和正常宫颈细胞（Ect1/E6E7）的生长。我们的研究结果表明，脆拟杆菌对 SiHa 细胞的抑制作用与各种生物学过程有关，特别是铁死亡途径。具体来说，我们发现脆拟杆菌通过 SiHa 细胞调节 HMOX1、SLC39A14、VDAC2、ACSL4 和 LPCAT3 等蛋白质的表达，这些蛋白质与铁死亡密切相关。此外，它还激活了 SiHa 细胞中的三羧酸（TCA）循环，导致活性氧（ROS）和脂质过氧化物（LPO）水平升高。这些结果揭示了脆拟杆菌在针对宫颈癌治疗中铁死亡途径的治疗潜力，为宫颈癌的研究和治疗开辟了新的途径。
