The induction of ferroptosis by impairing STAT3/Nrf2/GPx4 signaling enhances the sensitivity of osteosarcoma cells to cisplatin

Cell Biology International
Qiang Liu, Kunzheng Wang

Abstract

Recent studies have indicated that promoting ferroptosis is a promising approach to attenuate drug resistance of cancer cells. Hence, this study aimed to induce ferroptosis in osteosarcoma cells, thereby increasing the sensitivity to cisplatin. Osteosarcoma cells MG63 and Saos-2 were incubated with increasing doses of cisplatin to generate cisplatin-resistant strains, MG63/DDP and Saos-2/DDP. 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and flow cytometry assays were performed to evaluate cell proliferation and cell death, respectively. Malondialdehyde (MDA), reactive oxygen species (ROS), and lipid oxidation in cells were measured to evaluate the degree of cell ferroptosis. MG63/DDP and Saos-2/DDP cells showed increased viability and decreased death rate compared with MG63 and Saos-2 cells, respectively, upon cisplatin treatment. Western blotting analysis indicated that protein levels of p-STAT3 (Ser727), nuclear factor erythroid 2-related factor 2 (Nrf2), and glutathione peroxidase 4 (GPx4) in drug-resistant strains increased significantly in response to cisplatin. Co-treatment with cisplatin and agonists of ferroptosis, Erastin, and RSL3, remarkably increased MDA, ROS, lipid oxidation, and sensitivity t...Continue Reading

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Citations

Jun 5, 2020·Journal of Receptor and Signal Transduction Research·Zengjun XieLiang Zhao
Jan 11, 2020·Frontiers in Oncology·Hai-Hong ZhouXiao-Jian Yan
Oct 6, 2020·Oxidative Medicine and Cellular Longevity·Zhuanzhuan QiangHong Jiang
Oct 8, 2020·Biomarker Research·Sipeng ZuoLinna Lu
Jan 1, 2021·Cell Proliferation·Yun LiuJiake Xu
Jan 16, 2021·Journal of Veterinary Diagnostic Investigation : Official Publication of the American Association of Veterinary Laboratory Diagnosticians, Inc·Jordan AyersMarc Salute
Jan 1, 2021·Biomedicine & Pharmacotherapy = Biomédecine & Pharmacothérapie·Sepideh MirzaeiHaroon Khan
Mar 5, 2021·Biochemical and Biophysical Research Communications·Shi-Hua DengYing Xu
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Feb 12, 2021·Biomedicine & Pharmacotherapy = Biomédecine & Pharmacothérapie·Bowen LiHangyu Li
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Jan 19, 2022·Free Radical Research·Zhengquan XuWeihong Xu
Aug 11, 2021·Current Medicinal Chemistry·Erva Ozkan, Filiz Bakar-Ates

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