Fuzheng Yiliu Decoction-Medicated Serum Promotes Ferroptosis in Prostate Cancer Cells via PPARγ-PLIN2 Pathway

Abstract

Background: Prostate cancer (PCa) is the second most prevalent malignancy worldwide, yet effective treatment options remain limited. Fuzheng Yiliu decoction (FZYL), a traditional Chinese medicine (TCM) formula, exhibits anti-tumor properties, its mechanism of action in PCa is poorly understood. This study aimed to elucidate the therapeutic potential and underlying molecular mechanisms of FZYL-medicated serum in PCa treatment.

Methods: FZYL-medicated serum was prepared and applied to PCa cells (DU145 and PC3). Cell proliferation and apoptosis were assessed using cell counting kit-8 (CCK-8), propidium iodide (PI) staining, and TdT-mediated dUTP nick-end labeling (TUNEL) assay. Further the treated PCa cells were used for isobaric tags for relative and absolute quantification (iTRAQ)-based proteomic analysis. Perilipin 2 (pLIN2) and peroxisome proliferator-activated receptor gamma (PPARγ) levels were evaluated via qRT-PCR and western blot. Dual-luciferase reporter gene assay was employed to confirm the binding between pLIN2 and PPARγ. Ferroptosis markers, including reactive oxygen species (ROS), Fe²⁺, glutathione (GSH), and malondialdehyde (MDA) were measured.

Results: FZYL-medicated serum significantly inhibited DU145 and PC3 cell proliferation and induced apoptosis. Proteomic analysis revealed activation of the PPARγ-pLIN2 pathway, with pLIN2 transcription being regulated by PPARγ. Futherover, FZYL-medicated serum enhanced ferroptosis sensitivity, as evidenced by elevated ROSFe²⁺ and MDA levels and reduced GSH level. Overexpression of pLIN2 similarly promoted ferroptosis, confirming the pathway’s involvement.

Conclusions: Our findings demonstrated that FZYL-medicated serum induces ferroptosis in PCa cells through the PPARγ-pLIN2 pathway, providing a novel therapeutic strategy for PCa treatment.