Gang He
1,2* 
, Mei Liu
1, Tang cong Chen, Li fen Huang
1, You qiang Ke
1,21 Key Laboratory of Medicinal and Edible Plants Resources Development of Sichuan Education Department, Sichuan Industrial Institute of Antibiotics, School of Pharmacy, Chengdu University, Chengdu, China
2 Antibiotics Research and Re-evaluation Key Laboratory of Sichuan Province, Sichuan Industrial Institute of Antibiotics, School of Pharmacy, Chengdu University, Chengdu, China
Abstract
Introduction: Fatty acid binding protein 5 (FABP5) exhibits heightened expression levels in triple-negative breast cancer. The inhibitor of FABP5, Stony Brook fatty acid‐binding protein inhibitor 26 (SBFI-26), has demonstrated the capacity to suppress cell proliferation, migration, and invasion. This study delves into the functional mechanism and impact of combining SBFI-26 with docetaxel in treating MDA-MB-231 cells of triple-negative breast cancer.
Methods: Various concentrations of docetaxel and SBFI-26 were chosen for individual or combined treatments. The effects of SBFI-26, docetaxel, or their combination on cell cycle arrest and apoptosis were assessed using flow cytometry. Western blotting was utilised to detect the expression of apoptosis-related proteins, namely cysteinyl aspartate-specific proteases 3 (Caspase3), B cell leukemia/lymphoma 2 (Bcl-2), and Bcl-2 associated X (Bax), while intracellular reactive oxygen species (ROS) levels were determined using a fluorescence spectrophotometer.
Results: The IC50 values for SBFI-26 and docetaxel in inhibiting MDA-MB-231 cells were determined to be 106.1 μM and 86.14 nM, respectively. Significantly, the combination treatment augmented the proportion of G1 phase (apoptotic) cells by 3.67-fold compared to the control group (P < 0.0001). Furthermore, the apoptosis rate in the combination group was 2.59-fold higher than that in the docetaxel group (P < 0.0001) and demonstrated a significant increase of 1.82-fold compared with the SBFI-26 group (P < 0.001). Analyses revealed a decrease in the protein expression of Bcl-2, while Bax and Caspase3 exhibited an increase in the combination group for MDA-MB-231 cells. Moreover, the combined treatment group demonstrated a 2.97-fold increase (P < 0.0001) in ROS fluorescence intensity compared to the control group, a noteworthy 1.39-fold increase (P < 0.01) compared to the SBFI-26 treatment group, and a substantial 1.70-fold increase (P < 0.0001) compared to the docetaxel treatment group.
Conclusion: These findings suggest that the co-administration of SBFI-26 with docetaxel effectively enhances apoptosis in triple-negative breast cancer MDA-MB-231 cells by elevating intracellular ROS levels.