Prostate cancer (PCa) is the second most common malignancy in men worldwide. While androgen-deprivation therapy is the primary treatment, many patients inevitably progress to castration-resistant prostate cancer. The molecular mechanisms driving this progression are complex, necessitating the identification of new, effective, and safe therapeutic targets.
A research team led by Professor Jun Zhang from Shihezi University School of Medicine, China, focused on the transcription factor Krüppel-like factor 7 (KLF7). Their findings were made available online on July 15, 2026, in the Chinese Medical Journal . Through RNA sequencing and bioinformatics analysis, the team discovered that KLF7 is highly expressed in PCa and acts as a direct transcriptional activator of L1 cell adhesion molecule (L1CAM), a key protein associated with tumor metastasis. Furthermore, the study elucidated that the phosphorylation of the NF-κB p65 subunit acts as the master regulator of this axis.
Utilizing surface plasmon resonance and molecular docking, the researchers confirmed that gallic acid (GA) forms a stable complex with NF-κB p65, specifically targeting the serine 276 phosphorylation site. By inhibiting this phosphorylation, GA effectively blocks the downstream KLF7/L1CAM pathway.
In vitro experiments showed that GA significantly impaired the aggressive behaviors of PC-3 and LNCaP cells without exhibiting toxicity to normal prostate stromal cells. In vivo, using a high-fat-diet-induced obesity mouse model, the team demonstrated that GA administration significantly reduced tumor volume and weight. Remarkably, the anti-tumor efficacy of GA was comparable to conventional drugs like enzalutamide and bicalutamide, and combination therapy showed enhanced therapeutic outcomes. This study provides a strong theoretical basis for the clinical application of GA as a safe and potent agent against advanced PCa.
