Astragaloside IV-PESV inhibits prostate cancer tumor growth by restoring gut microbiota and microbial metabolic homeostasis via the AGE-RAGE pathway
Abstract 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 develo...
| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2024-04-01
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| Series: | BMC Cancer |
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| Online Access: | https://doi.org/10.1186/s12885-024-12167-z |
| _version_ | 1797199399109001216 |
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| author | Xujun You Junfeng Qiu Qixin Li Qing Zhang Wen Sheng Yiguo Cao Wei Fu |
| author_facet | Xujun You Junfeng Qiu Qixin Li Qing Zhang Wen Sheng Yiguo Cao Wei Fu |
| author_sort | Xujun You |
| collection | DOAJ |
| description | Abstract 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. |
| first_indexed | 2024-04-24T07:15:08Z |
| format | Article |
| id | doaj.art-5b7f7e77b1774446afb9afa848348cd0 |
| institution | Directory Open Access Journal |
| issn | 1471-2407 |
| language | English |
| last_indexed | 2024-04-24T07:15:08Z |
| publishDate | 2024-04-01 |
| publisher | BMC |
| record_format | Article |
| series | BMC Cancer |
| spelling | doaj.art-5b7f7e77b1774446afb9afa848348cd02024-04-21T11:21:38ZengBMCBMC Cancer1471-24072024-04-0124111210.1186/s12885-024-12167-zAstragaloside IV-PESV inhibits prostate cancer tumor growth by restoring gut microbiota and microbial metabolic homeostasis via the AGE-RAGE pathwayXujun You0Junfeng Qiu1Qixin Li2Qing Zhang3Wen Sheng4Yiguo Cao5Wei Fu6Department of Andrology, Shenzhen Bao’an Traditional Chinese Medicine Hospital, Guangzhou University of Chinese MedicineDepartment of Andrology, Shenzhen Traditional Chinese Medicine Hospital, Guangzhou University of Chinese MedicineDepartment of Andrology, Shenzhen Bao’an Traditional Chinese Medicine Hospital, Guangzhou University of Chinese MedicineDepartment of Andrology, Shenzhen Bao’an Traditional Chinese Medicine Hospital, Guangzhou University of Chinese MedicineSchool of Rehabilitation Medicine and Health Care, Hunan University of MedicineDepartment of Urology Surgery, Shenzhen Bao’an Traditional Chinese Medicine Hospital, Guangzhou University of Chinese MedicineDepartment of Andrology, Shenzhen Bao’an Traditional Chinese Medicine Hospital, Guangzhou University of Chinese MedicineAbstract 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.https://doi.org/10.1186/s12885-024-12167-zProstate cancerAstragaloside IVPESVAGE-RAGE |
| spellingShingle | Xujun You Junfeng Qiu Qixin Li Qing Zhang Wen Sheng Yiguo Cao Wei Fu Astragaloside IV-PESV inhibits prostate cancer tumor growth by restoring gut microbiota and microbial metabolic homeostasis via the AGE-RAGE pathway BMC Cancer Prostate cancer Astragaloside IV PESV AGE-RAGE |
| title | Astragaloside IV-PESV inhibits prostate cancer tumor growth by restoring gut microbiota and microbial metabolic homeostasis via the AGE-RAGE pathway |
| title_full | Astragaloside IV-PESV inhibits prostate cancer tumor growth by restoring gut microbiota and microbial metabolic homeostasis via the AGE-RAGE pathway |
| title_fullStr | Astragaloside IV-PESV inhibits prostate cancer tumor growth by restoring gut microbiota and microbial metabolic homeostasis via the AGE-RAGE pathway |
| title_full_unstemmed | Astragaloside IV-PESV inhibits prostate cancer tumor growth by restoring gut microbiota and microbial metabolic homeostasis via the AGE-RAGE pathway |
| title_short | Astragaloside IV-PESV inhibits prostate cancer tumor growth by restoring gut microbiota and microbial metabolic homeostasis via the AGE-RAGE pathway |
| title_sort | astragaloside iv pesv inhibits prostate cancer tumor growth by restoring gut microbiota and microbial metabolic homeostasis via the age rage pathway |
| topic | Prostate cancer Astragaloside IV PESV AGE-RAGE |
| url | https://doi.org/10.1186/s12885-024-12167-z |
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