FABP5 in CESC counteracts drug-induced ROS-mediated cytotoxicity by regulating fatty acid β-oxidation

Background Recent studies have demonstrated that FABP5 is highly expressed in various tumor cell types and associated with cancer progression, exerting cancerpromoting. It is also associated with resistance to multiple clinical chemotherapy drugs. Nevertheless, there is currently no report on the presence of the association between cervical cancer FABP5 and reactive oxygen species (ROS) induced by clinical chemotherapy drugs. Method In this study, we conducted data analysis using the TCGA databases to investigate the expression of FABP5 in cervical cancer. Additionally, we performed immunohistochemical staining on clinical pathological specimens and conducted in vitro cellular assays to validate our findings. In this study, commonly used clinical chemotherapy drugs-cisplatin and paclitaxel were employed as drug-induced ROS models. Result Our findings reveal that FABP5 expression is significantly upregulated in Cervical squamous cell carcinoma (CESC) compared to normal tissue and other cervical cancer histological types. Meanwhile, our study demonstrated that FABP5 exerted a crucial function in promoting the capacity of cervical cancer cells to proliferate, migrate and invade. Importantly, FABP5 exerts resistance to both cisplatin and paclitaxel, irrespective of the drug type. Additionally, We found that cells overexpressing FABP5 exhibit enhanced fatty acid storage capacity, reduced β-oxidation capacity, decreased ATP5A1-driven respiratory chain activity, and maintain a low ROS state. Conclusion FABP5 reduces fatty acid β-oxidation by altering metabolic pathways, thereby increasing tumor cell reserves and maintaining tumor cells in a low ROS state. This confers cellular tolerance to exogenous drug-induced ROS, potentially serving as a key factor contributing to the poor response of CESCs to drug therapy.