The Combinatorial Effect of Salt with IL-17 on HIF 1 Alpha and VEGF-A Expression in Breast Cancer Cells
Chronic inflammation is one of the major underlying reasons for progression and proliferation of different cancers. Studies have found that high concentration of salt (sodium chloride) promotes chronic inflammation. This study involves the investigation of synergistic effect of high concentration of sodium chloride and interleukin(IL)-17 in the induction of factors responsible for inflammation, angiogenesis such as vascular endothelial growth factor-A (VEGF-A) and the Hypoxia-inducible factors (HIFs). The treatment of breast cancer cell line (MCF-7) with high salt ( 0.2 M NaCl ) stimulated the production of VEGF-A 2.9 fold, and treatment with sub-minimal IL-17 (1 ng/ml) induced 2.6 fold increase (P<0.05) as compared to the untreated cells. While, the co-treatment of NaCl and IL-17 caused the 5.9-fold increased expression of VEGF-A (P<0.01), which suggested a synergistic role of these two factors in the production of VEGF-A and HIFs. Upon further investigation, it was found that high salt concentration induces the expression of VEGF-A through the activation of nuclear factor of activated T-cells (NFAT-5), and IL-17 stimulates expression of VEGF-A by activating the signal transducer and activator of transcription (STAT-3) signaling pathway. Furthermore, treating the normal human aortic endothelial cells with the supernatant of activated MCF-7 cells enhanced both the cell migration and the expression of factors responsible for cellular migration, such as β1 integrin, vascular cell adhesion protein, and cluster of differentiation (CD31). These findings have suggested the role of high concentration of salt and pro-inflammatory IL-17 in promoting the progression and metastasis of cancers. To conclude, these findings can have a potential role in cancer therapies low-salt diet, anti-NFAT5 and anti-STAT3 may provide novel avenues for enhanced efficiency of the current cancer therapy.
Dalal Abdullah Alotaibi,
"The Combinatorial Effect of Salt with IL-17 on HIF 1 Alpha and VEGF-A Expression in Breast Cancer Cells"
ETD Collection for Tennessee State University.