Department of Medical Genetics, China Medical University, Shenyang, 110122, Liaoning, China.
Department of Medical Genetics, China Medical University, Shenyang, 110122, Liaoning, China; Department of Obstetrics and Gynecology, Shengjing Hospital, China Medical University, Shenyang, 110004, Liaoning, China.
Biochem Biophys Res Commun. 2020 May 28;526(2):293-299. doi: 10.1016/j.bbrc.2020.03.079. Epub 2020 Mar 21.
Ferroptosis is an iron-dependent form of regulated cell death. GDF15 affects various properties of cancer cells, but the role of GDF15 in ferroptosis has not been reported. In the present study, we found that GDF15 knockdown led to decreased expression of SLC7A11, which is a key component of system X and a regulator of ferroptosis, indicating that GDF15 might play important roles in ferroptosis. CCK8 assay showed that GDF15 knockdown promoted erastin-induced ferroptosis in MGC803 cells. qRT-PCR and western blotting results demonstrated that GDF15 inhibition attenuated the increased SLC7A11 expression induced by erastin. Further study revealed that GDF15 knockdown promoted the decreased level of extracellular glutamate and intracellular GSH as well as the increased level of lipid ROS in the presence of erastin in MGC803 cells. Overall, the study shows that GDF15 knockdown promotes erastin-induced ferroptosis in MGC803 cells by attenuating the expression of SLC7A11 and the function of system X.
铁死亡是一种依赖铁的细胞程序性死亡方式。GDF15 影响癌细胞的多种特性，但 GDF15 对铁死亡的作用尚未报道。在本研究中，我们发现 GDF15 敲低导致 SLC7A11 的表达降低，SLC7A11 是系统 X 的关键组成部分和铁死亡的调节剂，表明 GDF15 可能在铁死亡中发挥重要作用。CCK8 检测表明，GDF15 敲低促进了 erastin 诱导的 MGC803 细胞铁死亡。qRT-PCR 和 Western blot 结果表明，GDF15 抑制减弱了 erastin 诱导的 SLC7A11 表达增加。进一步的研究表明，在 erastin 存在的情况下，GDF15 敲低促进了 MGC803 细胞中细胞外谷氨酸和细胞内 GSH 水平的降低以及脂质 ROS 水平的升高。总之，该研究表明 GDF15 敲低通过减弱 SLC7A11 的表达和系统 X 的功能促进 erastin 诱导的 MGC803 细胞铁死亡。
