Abstract

The growth of cancer is one of the many physiological and pathological processes that depend on ferroptosis, an iron-dependent kind of programmed cell death. This study examines how ferroptosis is regulated and how it affects the development of hepatocellular carcinoma (HCC) by means of the sterol carrier protein 2 (SCP2)/heat shock protein family B (small) member 1 (HSPB1) axis. The effects of SCP2 overexpression and the ferroptosis inhibitor Ferrostain-1 on cell viability, proliferation, invasion, and the expression of HSPB1 and ferroptosis-related genes were evaluated using cell counting kit-8 (CCK-8) assays, 5-Ethynyl-2'-deoxyuridine (EdU) assays, transwell assays, and protein expression analysis. Overexpression experiments were conducted to further explore the impact of HSPB1 and SCP2 on HCC cell function and ferroptosis. In HCC cell lines, overexpression of SCP2 significantly inhibited cell proliferation and invasion, while enhancing ferroptosis through the upregulation of malondialdehyde (MDA) and downregulation of antioxidant proteins glutathione peroxidase 4 (GPX4) and solute carrier family 7 member 11 (SLC7A11) and nuclear factor erythroid 2-related factor 2 (Nrf2). Notably, overexpression of HSPB1 reversed the effects of SCP2 on the viability, proliferation, invasion and ferroptosis of HCC cells. The SCP2/HSPB1 axis plays a crucial role in HCC progression, SCP2 inhibits the progression of HCC by suppressing the expression of HSPB1 to inducing ferroptosis. According to our results, focusing on the SCP2/HSPB1 axis may offer a unique treatment strategy to manage the evolution of HCC and get past ferroptosis-related resistance.