Abstract
Abstract Objectives To determine the effects of hypoxia-inducible factors (HIF)-1 inhibitors on carbonic anhydrase-IX (CA-IX) enzyme and vascular endothelial growth factor (VEGF) in melanoma. The HIF-1 pathway induces tumor growth and metastasis by stimulating the expression of CA-IX enzyme and VEGF proteins. Methods We evaluated the inhibition effects of Acriflavine and Echinomycin on CA-IX enzyme and VEGF in WM115 (primary) and SKMEL30 (metastatic) cell lines in normoxic and hypoxic conditions with Enzyme Linked Immunosorbent Assay. The cytotoxic activity of HIF-1 inhibitors was performed by using WST-1 assay. All experiments were performed at 450 nm using Epoch™ Microplate Spectrophotometer. Results IC50 values were observed with a concentration of 3 μmol/L for Echinomycin and Acriflavine in the WST-1 assay. Decreased CA-IX and VEGF levels were determined in both normoxia and hypoxia after inhibitors’ treatment with WM115 and SKMEL30 cell lines (p<0.05). Inhibitory effect of HIF-1 inhibitors on CA-IX and VEGF proteins was observed in cell lines WM115 and SKMEL30. Conclusions Due to the importance of our study, using HIF-1 inhibitors may be an alternative treatment for melanoma. Also to design new HIF-1 inhibitor derivatives is a promising approach for further studies targeting CA-IX enzyme and VEGF.
Highlights
Melanoma, a most common type of cancer, is derived from melanocyte cells and the field has seen an unprecedented set of clinical advances in recent years [1]
Inhibitory effect of hypoxia-inducible factors (HIF)-1 inhibitors on carbonic anhydrase-IX (CA-IX) and vascular endothelial growth factor (VEGF) proteins was observed in cell lines WM115 and SKMEL30
To design new HIF-1 inhibitor derivatives is a promising approach for further studies targeting CA-IX enzyme and VEGF
Summary
A most common type of cancer, is derived from melanocyte cells and the field has seen an unprecedented set of clinical advances in recent years [1]. Tumor hypoxia is related to cancer prognosis it is associated with aggressive growth and metastasis [4]. HIF-1α is responsible for the prognosis in many tumors such as gastric, bladder, breast, colorectal and melanoma [5]. They could be candidates as a potential therapeutic key in the progression and aggressiveness of cancer comparing with conventional therapies such as chemotherapy or radiation therapy [6]. CA-IX promotes metastasis by stimulating the acidification in the tumor microenvironment in melanoma and VEGF-mediated angiogenesis is managed to promote the progression of melanoma by hypoxia [8]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
