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The Colon-26 Carcinoma Tumor-bearing Mouse as a Model for the Study of Cancer Cachexia
Published on: November 30, 2016
Li-ginseng powder alleviates cancer cachexia in mice by regulating the ubiquitin-proteasome pathway and reducing
Xinghui Jin1,2, Wenyuan Liu1, Gang-Ao Li1,2
1Key Laboratory for Molecular Enzymology and Engineering of the Ministry of Education, School of Life Sciences, Jilin University, Changchun, 130012, China.
Background:
As a debilitating syndrome, cancer cachexia (CC) manifests as ongoing weight reduction and skeletal muscle atrophy, which severely compromise patients' well-being and life expectancy, with no approved treatment available to date. Rare ginsenosides such as Rh2, Rg5, Rk1, and Rh4 have been reported to modulate Nuclear factor kappa-B (NF-κB) and Signal Transducer and Activator of Transcription 3 (STAT3) activity and attenuate inflammatory signaling pathways implicated in CC progression. Li-Ginseng powder (LGP), a specially processed Panax ginseng enriched in rare ginsenosides, including Rk1, Rk3, Rh4, Rg3, and Rg5 represents a potential therapeutic candidate for CC.
Methods:
The anti-cachexia effects of LGP were evaluated in a BALB/c mouse model of CC and in a cellular CC model using mouse myoblast C2C12 cells. Body weight, skeletal muscle atrophy, and histopathological analyses were performed to assess in vivo efficacy. Network pharmacology was applied to predict key regulatory pathways, and mechanistic validation was conducted using Western blotting, immunohistochemistry, and Enzyme-linked immunosorbent assay.
Results:
LGP treatment significantly attenuated body weight loss and skeletal muscle atrophy in CC mice. Mechanistically, LGP suppressed activation of the ubiquitin-proteasome pathway in the gastrocnemius muscle and reduced systemic and local inflammatory responses. Network pharmacology analysis identified NF-κB and STAT3 signaling as major targets of LGP, which was further confirmed in both muscle tissues and C2C12 cells. Consistently, LGP alleviated myotube atrophy and inhibited UPP, NF-κB, and STAT3 activation in vitro.
Conclusion:
These findings demonstrate that LGP exerts protective effects against CC by modulating muscle proteolysis and inflammation-related signaling pathways, highlighting its potential as a ginseng-based therapeutic strategy for CC.
Insights
Li-Ginseng powder (LGP) combats cancer cachexia (CC) by reducing weight loss and muscle atrophy. It works by inhibiting inflammation and the ubiquitin-proteasome pathway, targeting key signaling pathways like NF-κB and STAT3.
Area of Science:
- Biomedical Science
- Pharmacology
- Molecular Biology
Background:
- Cancer cachexia (CC) is a debilitating syndrome characterized by weight loss and muscle atrophy, with no current approved treatments.
- Rare ginsenosides show potential in modulating inflammatory pathways (NF-κB, STAT3) implicated in CC.
- Li-Ginseng powder (LGP), derived from Panax ginseng and rich in rare ginsenosides, is a potential therapeutic candidate for CC.
Purpose of the Study:
- To evaluate the anti-cachexia effects of Li-Ginseng powder (LGP).
- To investigate the underlying mechanisms of LGP's action in cancer cachexia models.
- To explore LGP's potential as a novel therapeutic strategy for CC.
Main Methods:
- In vivo evaluation in a BALB/c mouse model of CC and in vitro using C2C12 myoblast cells.
- Assessment of body weight, skeletal muscle atrophy, and histopathology.
- Network pharmacology for pathway prediction, validated by Western blotting, immunohistochemistry, and ELISA.
Main Results:
- LGP treatment significantly reduced weight loss and skeletal muscle atrophy in CC mice.
- LGP suppressed the ubiquitin-proteasome pathway (UPP) and inflammatory responses in muscle tissue.
- Network pharmacology and experimental validation confirmed LGP targets NF-κB and STAT3 signaling pathways, alleviating myotube atrophy in vitro.
Conclusions:
- LGP demonstrates protective effects against cancer cachexia.
- LGP modulates muscle proteolysis and inflammation-related signaling pathways, including UPP, NF-κB, and STAT3.
- LGP represents a promising ginseng-based therapeutic strategy for managing CC.
