白藜芦醇 (Res) 是一种具有抗肿瘤活性的天然植物雌激素。本研究旨在探讨Res在口腔鳞状细胞癌（OSCC）铁死亡中的作用。用不同剂量的Res处理正常人口腔角质形成细胞（HOK）/口腔OSCC（CAL-27/SCC-9）细胞系。通过MTT法测定Res毒性，计算Res对CAL-27和SCC-9细胞的半数最大抑制浓度值。通过CCK-8/集落形成测定/transwell测定/流式细胞术评估细胞活力/集落形成效率/迁移/侵袭/周期。通过Western blot和RT-qPCR测定细胞核和细胞质中p53蛋白的表达、谷胱甘肽过氧化物酶4（GPX4）的表达以及SLC7A11信使RNA（mRNA）和蛋白的表达水平。评估Fe2+含量、活性氧（ROS）水平、还原型谷胱甘肽（GSH）和乳酸脱氢酶（LDH）释放。中低剂量Res对HOK细胞无毒性作用，而高剂量Res显着降低HOK细胞细胞活力。 Res 显着抑制 OSCC 细胞（CAL-27 和 SCC-9）的活力。 Res 抑制 OSCC 细胞集落形成/迁移/侵袭，并诱导 G1 期停滞。 Res引起p53蛋白易位至细胞核，明显增加Fe2+含量、ROS水平和LDH释放，降低GSH含量和GPX4蛋白表达，诱导铁死亡。 p53 的下调部分逆转了 Res 对 CAL-27 细胞恶性行为的抑制作用。 Res 通过促进 p53 进入细胞核来抑制 SLC7A11 转录。 SLC7A11 过表达否定了 p53 敲除对 Res 在 OSCC 细胞恶性行为和铁死亡中的调节作用。Res 通过调节 p53/SLC7A11 加速铁死亡并抑制 OSCC 细胞的恶性行为。© 2024。作者。

Resveratrol (Res) is a natural phytoestrogen with antitumor activity. This study sought to investigate the role of Res in ferroptosis in oral squamous cell carcinoma (OSCC).Normal human oral keratinocyte (HOK)/oral OSCC (CAL-27/SCC-9) cell lines were treated with different doses of Res. Res toxicity was determined by MTT assay, with half maximal inhibitory concentration values of Res on CAL-27 and SCC-9 cells calculated. Cell viability/colony formation efficiency/migration/invasion/cycle were assessed by CCK-8/colony formation assay/transwell assay/flow cytometry. The expression of p53 protein in the nucleus and cytoplasm, glutathione peroxidase 4 (GPX4) expression, and SLC7A11 messenger RNA (mRNA) and protein expression levels were determined by Western blot and RT-qPCR. Fe2+ content, reactive oxygen species (ROS) level, reduced glutathione (GSH), and lactate dehydrogenase (LDH) release were assessed.Medium- to low-dose Res had no toxic effect on HOK cells, while high-dose Res markedly reduced HOK cell viability. Res significantly suppressed the viability of OSCC cells (CAL-27 and SCC-9). Res inhibited OSCC cell colony formation/migration/invasion, and induced G1 phase arrest. Res caused the translocation of p53 protein to the nucleus, obviously increased Fe2+ content, ROS level and LDH release, decreased GSH content and GPX4 protein expression, and induced ferroptosis. Down-regulation of p53 partially reversed the inhibitory effects of Res on CAL-27 cell malignant behaviors. Res inhibited SLC7A11 transcription by promoting p53 entry into the nucleus. SLC7A11 overexpression negated the the regulatory effects of p53 knockout on the role of Res in OSCC cell malignant behaviors and ferroptosis.Res accelerated ferroptosis and inhibited malignant behaviors in OSCC cells by regulating p53/SLC7A11.© 2024. The Author(s).