Melatonin blunts the tumor-promoting effect of cancer-associated fibroblasts by reducing IL-8 expression and reversing epithelial-mesenchymal transition.
Int Immunopharmacol
; 119: 110194, 2023 Jun.
Article
in En
| MEDLINE
| ID: mdl-37080066
ABSTRACT
BACKGROUND:
Most studies on melatonin have focused on tumor cells but have ignored the tumor microenvironment (TME), especially one of its important components, the cancer-associated fibroblasts (CAFs). Therefore, we attempted to explore the role of melatonin in TME.METHODS:
We investigated the regulatory role of melatonin in the tumor-promoting effect of CAFs and its underlying mechanism by using cell and animal models.RESULTS:
CAFs promoted tumor progression, but melatonin weakened the tumor-promoting effect of CAFs. Compared with tumor cells, IL-8 was mainly expressed in CAFs. CAFs-overexpressing IL-8 induced the epithelial-mesenchymal transition (EMT) of tumor cells, and a positive crosstalk was observed between CAFs and tumor cells undergoing EMT, thereby further promoting the IL-8 expression. Melatonin suppressed this crosstalk by inhibiting the NF-κB pathway, thereby impeding the IL-8 expression from CAFs. Importantly, melatonin reversed CAFs-derived IL-8-mediated EMT by inhibiting the AKT pathway. Melatonin was found to directly and indirectly inhibit tumor progression.CONCLUSION:
Our research reveals the potential action mechanism of melatonin in regulating the CAF-tumor cell interaction and suggests the potential of melatonin as an adjuvant of tumor therapy.Key words
Full text:
1
Database:
MEDLINE
Main subject:
Cancer-Associated Fibroblasts
/
Melatonin
/
Neoplasms
Type of study:
Prognostic_studies
/
Risk_factors_studies
Language:
En
Journal:
Int Immunopharmacol
Year:
2023
Type:
Article
Affiliation country:
China