Background
Evidence indicates that chronic stress promotes progression of colorectal liver metastases (CLM). Mangiferin is the active chemical constituent of the rhizomes of Anemarrhena asphodeloides Bunge. Mangiferin (MGF) exerts anti-inflammatory, anti-proliferative, anti-angiogenic, anti-fibrotic and antioxidant effects in a variety of cancers. Its mechanism in chronic stress and tumor growth is still poorly understood.
Conclusion
MGF can alleviate CUMS induced tumor growth and the treatment of CLM patients with MGF may be beneficial.
Methods
To investigate the effects of MGF on the CLM and tumor-associated depression, activated hepatic stellate cells (a-HSCs), HT-29 CRC cells, were used in chronic unpredictable mild stress (CUMS) of tumor-bearing models. Potential antidepressant activity was determined by FST, TST, SIT and serum cytokine (IL-6, IL-18 and TNF-α) examination. Downstream signaling molecules were detected by Western blot, immunohistochemistry and fluorescence microscopy.
Results
CUMS induced depression behavior and depression-related cytokines and promoted tumor growth in CLM. MGF-treated mice significantly improved chronic stress behaviors by reducing depression-related cytokines. In addition, MGF treatment inhibits WAVE2 signaling pathway, leading to TGF-β1 induced HSC inhibition, thereby reducing depressive behavior and tumor growth in CLM.