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 IDF- 11774. 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.