Iron has been found to be involved in the tumor cell proliferation process, which can lead to the increased sensitivity of cancer cells to ferroptosis. Since erianin is associated with oxidative stress in hepatocellular carcinoma (HCC), we hypothesized that the therapeutic effect and mechanism of erianin on HCC is related to ferroptosis. HCC cells were stimulated with increase of erianin concentrations for 24 h, and the survival rates of Huh-7 and HepG2 cells gradually decreased. After intervention with different doses of erianin, cell proliferation, clone number, and invasion were prominently decreased, apoptosis ratio was increased. Moreover, Nec-1, CQ, and Z-VAD had no effect on the cell viability induced by erianin, while the combination of ferroptosis inhibitors (deferoxamine mesylate, ferrostatin-1, and liproxstatin-1) and erianin prominently increased cell survival rate. Erianin pretreatment induced ferroptosis by enhancing reactive oxygen species, MDA, and Fe²⁺ levels, and reducing GSH levels. Erianin activated JAK2/STAT3 pathway and inhibited SLC7A11 and GPX4 expression, thereby inducing ferroptosis. Besides, tumor growth was significantly inhibited in the erianin-treated mice, and there was no obvious toxicity in the mice. Erianin reduced proliferation and invasion of HCC cells by inducing ferroptosis by blocking the JAK2/STAT3/SLC7A11 pathway, thereby impeding tumor growth.

中文翻译：

---

毛兰素通过 JAK2/STAT3/SLC7A11 通路促进铁死亡并抑制肝细胞癌侵袭，从而抑制肿瘤生长


研究发现铁参与肿瘤细胞增殖过程，可导致癌细胞对铁死亡的敏感性增加。由于毛兰素与肝细胞癌（HCC）的氧化应激有关，因此我们推测毛兰素对HCC的治疗作用和机制与铁死亡有关。增加毛兰素浓度刺激HCC细胞24 h，Huh-7和HepG2细胞的存活率逐渐下降。不同剂量毛兰素干预后，细胞增殖、克隆数、侵袭能力均显着降低，凋亡率升高。此外，Nec-1、CQ和Z-VAD对毛兰素诱导的细胞活力没有影响，而铁死亡抑制剂（甲磺酸去铁胺、铁他汀-1和利普司他汀-1）与毛兰素的组合显着提高了细胞存活率。毛兰素预处理通过提高活性氧、MDA和Fe ²⁺水平并降低GSH水平诱导铁死亡。毛兰素激活JAK2/STAT3通路并抑制SLC7A11和GPX4表达，从而诱导铁死亡。此外，毛兰素治疗小鼠的肿瘤生长受到显着抑制，且对小鼠没有明显的毒性作用。毛兰素通过阻断 JAK2/STAT3/SLC7A11 通路诱导铁死亡，从而减少 HCC 细胞的增殖和侵袭，从而阻止肿瘤生长。