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The regulation of the VHLHIF pathway is also related to iron metabolism and ferroptosis in ccRCC, as iron levels are significantly higher in RCC cells and the tumor microenvironment than in normal renal tissue (77), and as HIF-1 mediates the cellular upregulation of TfRC and heme oxygenase (HO) expression, promoting cellular iron accumulation (78, 79)

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doi:10.1007/s40257-021-00595-7

However, when combined with Resveratrol (HY-16561), the cytotoxic effect induced by Copper (I) oxide is significantly attenuated, and oxidative damage is effectively alleviated