Department of Gastrointestinal Surgery, Guangxi Medical University Cancer Hospital, Guangxi Clinical Research Center for Colorectal Cancer, Nanning, 530021 Guangxi, China.
Department of Cancer Prevention and Control, Guangxi Medical University Cancer Hospital, Nanning, 530021 Guangxi, China.
Biomed Res Int. 2022 Aug 4;2022:6532253. doi: 10.1155/2022/6532253. eCollection 2022.
Gastric cancer (GC) is one of the most common gastrointestinal malignancies. Ferroptosis is a new type of peroxidation-driven and iron-dependent cell death. However, the biological functions and exact regulatory mechanisms of ferroptosis in GC remain elusive. Here, we performed RNAi and gene transfection, cell viability assay, lipid peroxidation assay, reactive oxygen species (ROS) assay, glutathione assay, qRT-PCR, Western blotting, and transmission electron microscopy (TEM) to study ferroptosis in gastric cancer. The results revealed that silencing latent transforming growth factor binding proteins (LTBP2) can significantly inhibit GC cell proliferation and decrease cellular GSH levels, reduce GPX4 activity, and increase ROS generation and malondialdehyde (MDA) levels, leading to ferroptosis in GC cells. In addition, we demonstrate that suppression of LTBP2 could regulate the p62-Keap1-Nrf2 pathway, thereby downregulating the GPX4 and xCT expression and upregulating the PTGS2 and 4HNE expression. Our findings described a new role of LTBP2 in regulating ferroptosis, which heralds the prospect of ferroptosis-mediated cancer therapy.
胃癌（GC）是最常见的胃肠道恶性肿瘤之一。铁死亡是一种新型的由过氧化物驱动和铁依赖性的细胞死亡。然而，铁死亡在 GC 中的生物学功能和确切的调节机制仍不清楚。在这里，我们通过 RNAi 和基因转染、细胞活力测定、脂质过氧化测定、活性氧（ROS）测定、谷胱甘肽测定、qRT-PCR、Western blot 和透射电子显微镜（TEM）来研究胃癌中的铁死亡。结果表明，沉默潜伏转化生长因子结合蛋白（LTBP2）可显著抑制 GC 细胞增殖，降低细胞内 GSH 水平，降低 GPX4 活性，增加 ROS 生成和丙二醛（MDA）水平，导致 GC 细胞发生铁死亡。此外，我们证明抑制 LTBP2 可以调节 p62-Keap1-Nrf2 通路，从而下调 GPX4 和 xCT 的表达，上调 PTGS2 和 4HNE 的表达。我们的研究结果描述了 LTBP2 在调节铁死亡中的新作用，为铁死亡介导的癌症治疗带来了新的前景。
