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.
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Reference
DOI: 10.1097/CM9.0000000000004202
Funding information
This work was supported by grants from the Tianshan Talent Project in Xinjiang Autonomous Region (Nos. 2023TSYCCX0116 and 2023TSYCQNTJ0032) and Scientific and Technological Research Project of Xinjiang Production and Construction Corps (Nos. 2025DA014 and 2025DB044).
Chinese Medical Journal
Experimental study
Gallic acid attenuates the malignant phenotype of prostate cancer cells by antagonizing NF-κB/KLF7/L1CAM expression
15-Jul-2026