Astragaloside
IV-PESV inhibits prostate cancer tumor growth by restoring gut
microbiota and microbial metabolic homeostasis via the AGE-RAGE pathwayXujun You, Junfeng Qiu, Qixin Li, Qing Zhang, Wen Sheng, Yiguo Cao, Wei Fu
BMC cancer 24 (1), 472, 2024
Background
Prostate cancer (PCa) is becoming the most common malignancy in men worldwide. We investigated the effect of astragaloside IV combined with PESV on the gut microbiota and metabolite of PCa mice and the process of treating
PCa.
Methods
Nude mice were genetically modified to develop tumors characteristic of PCa.
The treatment of PCa mice involved the administration of a combination
of astragaloside IV and peptides derived from scorpion venom (PESV).
Feces were collected for both 16 S rDNA and metabolic analysis. Fecal
supernatant was extracted and used for fecal transplantation in PCa
mice. Tumor development was observed in both PCa mice and nude mice.
Tumor histopathology was examined, and the expression of inflammatory
factors and the AGE-RAGE axis in PCa tissues were analyzed.
Results
PCa mice treated with Astragaloside IV in combination with PESV showed a
significant reduction in tumor volume and weight, and stabilization of
gut microbiota and metabolites. At the Genus level, significant
differences were observed in Porphyromonas, Corynebacterium, Arthromitus and Blautia, and the differential metabolites were PA16_016_0, Astragaloside+, Vitamin A acid, Nardosinone, a-Nortestoster, D-Pantethine, Hypoxanthine, Pregnenolone, cinnamic acid, Pyridoxa, Cirtruline and Xanthurenate.
There was a correlation between gut microbiota and metabolites. After
the fecal transplantation, tumor growth was effectively suppressed in
the PCa mice. Notably, both the mRNA and protein levels of the receptor
for advanced glycation end products (RAGE) were significantly decreased.
Furthermore, the expression of inflammatory factors, namely NF-κB,
TNF-α, and IL-6, in the tumor tissues was significantly attenuated.
Conversely, upregulation of RAGE led to increased inflammation and
reversed tumor growth in the mice.
Conclusion
Astragaloside IV combined with PESV could treat PCa by intervening in gut microbiota composition and metabolite by targeting RAGE.