Iron deficiency in hepatocellular carcinoma cells induced sorafenib resistance by upregulating HIF-1α to inhibit apoptosis

• DOI: 10.1016/j.biopha.2023.114750
• Publication Date: 2023-04-22T00:58:44Z
• Authors: Zelong Gao; Dongyao Wang; Jianxin Yang; Min Li; Changquan Ling; Diya Lv; Yan Cao; Zhenyu Chen; Ce Shi; Hui Shen; Yuxiao Tang
• Keywords: Malondialdehyde

Sorafenib is the first-line therapeutic agent for hepatocellular carcinoma (HCC), but drug resistance has become a major impediment. Previously we found that abnormal iron metabolism in HCC led to deficiency, whether it induces sorafenib during treatment of not yet disclosed. In this study, observed effects deficiency on and explored underlying mechanisms. The results revealed killing cells were weakened by effectively restored re-supplementation. ferroptosis indicators, including contents lipid hydroperoxide (LPO) malondialdehyde (MDA), level intracellular reactive oxygen species (ROS), expression glutathione peroxidase 4 (GPX4), significantly changed sorafenib-treated cells. However, sorafenib-induced apoptosis was inhibited deficiency. Notably, anti-apoptotic protein B-cell lymphoma-2 (BCL-2) elevated, expressions other apoptotic proteins, BCL2-associated X (Bax), caspase-3, caspase-9, Mechanistically, upregulated hypoxia-inducible factor 1 alpha (HIF-1α) increase BCL-2. Inhibition HIF-1α suppressed deficiency-induced BCL-2 resistance. summary, generated increasing BCL-2, which therefore These identified as new cells, would be an effective target alleviate