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http://dx.doi.org/10.4062/biomolther.2022.061

Anti-Tumor Effect of IDF-11774, an Inhibitor of Hypoxia-Inducible Factor-1, on Melanoma  

Kim, Nan-Hyung (Department of Dermatology, Dongguk University Ilsan Hospital)
Jeong, Jong Heon (Department of Dermatology, Dongguk University Ilsan Hospital)
Park, Yu Jeong (Department of Dermatology, Dongguk University Ilsan Hospital)
Shin, Hui Young (Department of Dermatology, Dongguk University Ilsan Hospital)
Choi, Woo Kyoung (Department of Dermatology, Dongguk University Ilsan Hospital)
Lee, Kyeong (BK21 FOUR Team and Integrated Research Institute for Drug Development, College of Pharmacy, Dongguk University)
Lee, Ai-Young (Department of Dermatology, Dongguk University Ilsan Hospital)
Publication Information
Biomolecules & Therapeutics / v.30, no.5, 2022 , pp. 465-472 More about this Journal
Abstract
Melanoma is one of the most aggressive skin cancers. Hypoxia contributes to the aggressiveness of melanoma by promoting cancer growth and metastasis. Upregulation of cyclin D1 can promote uncontrolled cell proliferation in melanoma, whereas stimulation of cytotoxic T cell activity can inhibit it. Epithelial mesenchymal transition (EMT) plays a critical role in melanoma metastasis. Hypoxia-inducible factor-1α (HIF-1α) is a main transcriptional mediator that regulates many genes related to hypoxia. CoCl2 is one of the most commonly used hypoxia-mimetic chemicals in cell culture. In this study, inhibitory effects of IDF-11774, an inhibitor of HIF-1α, on melanoma growth and metastasis were examined using cultured B16F10 mouse melanoma cells and nude mice transplanted with B16F10 melanoma cells in the presence or absence of CoCl2-induced hypoxia. IDF-11774 reduced HIF-1α upregulation and cell survival, but increased cytotoxicity of cultured melanoma cells under CoCl2-induced hypoxia. IDF-11774 also reduced tumor size and local invasion of B16F10 melanoma in nude mice along with HIF-1α downregulation. Expression levels of cyclin D1 in melanoma were increased by CoCl2 but decreased by IDF-11774. Apoptosis of melanoma cells and infiltration of cytotoxic T cells were increased in melanoma after treatment with IDF-11774. EMT was stimulated by CoCl2, but restored by IDF11774. Overall, IDF-11774 inhibited the growth and metastasis of B16F10 melanoma via HIF-1α downregulation. The growth of B16F10 melanoma was inhibited by cyclin D1 downregulation and cytotoxic T cell stimulation. Metastasis of B16F10 melanoma was inhibited by EMT suppression.
Keywords
$HIF-1{\alpha}$ inhibitor; Inhibition of melanoma growth and metastasis; IDF11774;
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