Objective: To investigate the effect of GPX4-mediated iron death on adriamycin sensitivity in breast cancer and its related molecular mechanism. Methods: qRT-PCR and western blot assay were used to explore the expression of GPX4 in the normal breast cells MCF10A and HCC1937 and the breast cancer cells MCF-7 and MDA-MB-231. Lentivirus transfection technique was used to construct MCF-7 breast cancer cell with stable knockdown of GPX4, and the knockdown efficiency was detected by qRT-PCR and western blot assay. CCK8 assay was used to detect the sensitivity of breast cancer cells to adriamycin. The GSH concentration, MDA level and iron ion level of breast cancer cells after GPX4 knockdown were detected by GSH detection kit, MDA detection kit and iron ion concentration detection kit. Results: The expression of GPX4 in breast cancer cells was significantly higher than those in normal breast cells. Knockdown of GPX4 significantly reduced the level of GSH, promoted the levels of MDA and Fe2+, and significantly enhanced the sensitivity of GPX4 to adriamycin in breast cancer cells, while ferrostatin 1 reversed the sensitivity of GPX4 to adriamycin in breast cancer cells. Conclusion: Silencing GPX4 can promote the ferroptosis of breast cancer cells, and ultimately promote the sensitivity of breast cancer to adriamycin.
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