[Sanguinarine induces ferroptosis of colorectal cancer cells by upregulating STUB1 and downregulating GPX4].

Y Zhang, Z Luo, R Zhao, N Zhao, Z Xu, D Ao, G Cong, X Liu, H Zheng
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Abstract

Objective: To investigate the effect of sanguinarine (SAN) on proliferation and ferroptosis of colorectal cancer cells.

Methods: SW620 and HCT-116 cells treated with different concentrations of SAN were examined for cell viability changes using CCK8 assay to determine the IC50 of SAN in the two cells. The inhibitory effects of SAN on proliferation, invasion and migration of the cells were evaluated using colony-forming assay and Transwell assays. ROS production in the treated cells was analyzed with flow cytometry, and lipid peroxide production was assessed by detecting malondialdehyde (MDA) level. Glutathione (GSH) levels in the cells were detected, and Western blotting was used to detect the expressions of ferroptosis-related proteins STUB1 and GPX4.

Results: SAN significantly inhibited the proliferation, invasion and migration of SW620 and HCT-116 cells. SAN treatment significantly promoted ROS production, increased intracellular MDA level, and lowered GSH level in the two cells (P<0.05). Western blotting showed that SAN significantly upregulated the expression of STUB1 and down-regulated the expression of its downstream protein GPX4 (P<0.05).

Conclusion: SAN induces ferroptosis in colorectal cancer cells by regulating STUB1/GPX4, which may serve as a new therapeutic target for colorectal cancer.

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[番荔枝碱通过上调 STUB1 和下调 GPX4 诱导结直肠癌细胞的铁变态反应】。]
目的研究山金车花碱(SAN)对结直肠癌细胞增殖和铁变态反应的影响:方法:用 CCK8 检测法检测经不同浓度 SAN 处理的 SW620 和 HCT-116 细胞的活力变化,以确定 SAN 在两种细胞中的 IC50。利用集落形成试验和 Transwell 试验评估了 SAN 对细胞增殖、侵袭和迁移的抑制作用。用流式细胞仪分析了处理细胞中 ROS 的产生情况,并通过检测丙二醛(MDA)水平评估了过氧化脂质的产生情况。检测细胞中谷胱甘肽(GSH)的水平,并用 Western 印迹法检测铁突变相关蛋白 STUB1 和 GPX4 的表达:结果:SAN能明显抑制SW620和HCT-116细胞的增殖、侵袭和迁移。结果:SAN 能明显抑制 SW620 和 HCT-116 细胞的增殖、侵袭和迁移;SAN 处理能明显促进 ROS 的产生、细胞内 MDA 水平的升高和 GSH 水平的降低(PPConclusion:SAN通过调节STUB1/GPX4诱导结直肠癌细胞的铁变态反应,可作为结直肠癌的新治疗靶点。
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208
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