The aryl hydrocarbon receptor (AhR) is a liganddependent transcription factor whose activity is modulated by xenobiotics and physiological ligands. Activation of the AhR by environmental xenobiotics may induce a conformational change in AhR and has been implicated in a variety of cellular processes, including inflammation and tumorigenesis. It is unknown whether the activation of AhR serves a role in modulating the progression of osteosarcoma. The osteosarcoma cell line MG-63, was treated with AhR ligand, 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). TCDD treatment degrades AhR expression through activation of the AhR signaling pathway, however there were no survival differences observed in MG-63 cells. There were concomitant elevations of cyclooxygenase-2 and receptor activator of nuclear factor-κB ligand secretion from MG-63 cells upon TCDD treatment on a protein and mRNA level at 24 and 72 h. In addition, TCDD treatment also increases the production of prostaglandin E2 on MG-63 cells, and induces the expression of chemokine receptor CXCR4. However, CXCL12 production was not altered in MG-63 cells when stimulated with TCDD. The AhR antagonist CH-223191, blocks the effects on TCDD-induced RANKL, COX-2, PGE2 and CXCR4 changes. In conclusion, these findings suggest that AhR signal therapy should be further explored as a therapeutic option for the treatment of osteosarcoma.
- Aryl hydrocarbon receptor
- Receptor activator of nuclear factor κΒ ligand
ASJC Scopus subject areas
- Cancer Research