title: Long-Term Alteration of Reactive Oxygen Species Led to Multidrug Resistance in MCF-7 Cells.
abstract: Reactive oxygen species (ROS) play an important role in multidrug resistance (MDR). This study aimed to investigate the effects of long-term ROS alteration on MDR in MCF-7 cells and to explore its underlying mechanism. Our study showed both long-term treatments of H2O2and glutathione (GSH) led to MDR with suppressed iROS levels in MCF-7 cells. Moreover, the MDR cells induced by 0.1μM H2O2treatment for 20 weeks (MCF-7/ROS cells) had a higher viability and proliferative ability than the control MCF-7 cells. MCF-7/ROS cells also showed higher activity or content of intracellular antioxidants like glutathione peroxidase (GPx), GSH, superoxide dismutase (SOD), and catalase (CAT). Importantly, MCF-7/ROS cells were characterized by overexpression of MDR-related protein 1 (MRP1) and P-glycoprotein (P-gp), as well as their regulators NF-E2-related factor 2 (Nrf2), hypoxia-inducible factor 1 (HIF-1α), and the activation of PI3K/Akt pathway in upstream. Moreover, several typical MDR mediators, including glutathione S-transferase-π(GST-π) and c-Myc and Protein Kinase Cα(PKCα), were also found to be upregulated in MCF-7/ROS cells. Collectively, our results suggest that ROS may be critical in the generation of MDR, which may provide new insights into understanding of mechanisms of MDR.
authors.affiliation: Key Laboratory of Natural Medicine and Immune Engineering, Henan University, Kaifeng, China.
authors.forename: Juan
authors.initials: J
authors.lastname: Cen
authors.affiliation: Key Laboratory of Natural Medicine and Immune Engineering, Henan University, Kaifeng, China.
authors.forename: Li
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Key Laboratory of Natural Medicine and Immune Engineering, Henan University, Kaifeng, China.
authors.forename: Fangfang
authors.initials: F
authors.lastname: Liu
authors.affiliation: School of Pharmacy, Henan University, Kaifeng, China.
authors.forename: Feng
authors.identifier: 0000-0001-7414-0450
authors.initials: F
authors.lastname: Zhang
authors.affiliation: Key Laboratory of Natural Medicine and Immune Engineering, Henan University, Kaifeng, China.
authors.forename: Bian-Sheng
authors.identifier: 0000-0001-9203-9663
authors.initials: BS
authors.lastname: Ji
mesh_terms: D000975:Antioxidants / Q000378:metabolism; D001692:Biological Transport / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D004317:Doxorubicin / Q000494:pharmacology; D018432:Drug Resistance, Multiple / Q000187:drug effects*; D019008:Drug Resistance, Neoplasm / Q000187:drug effects*; D005978:Glutathione / Q000494:pharmacology; D006801:Humans; D006861:Hydrogen Peroxide / Q000494:pharmacology; D042541:Intracellular Space / Q000378:metabolism; D061986:MCF-7 Cells; D008954:Models, Biological; D017382:Reactive Oxygen Species / Q000494:pharmacology*; D020112:Rhodamine 123 / Q000494:pharmacology; D015398:Signal Transduction / Q000187:drug effects; D013997:Time Factors; D015854:Up-Regulation / Q000187:drug effects
chemical_list: D000975:Antioxidants; D017382:Reactive Oxygen Species; D020112:Rhodamine 123; D004317:Doxorubicin; D006861:Hydrogen Peroxide; D005978:Glutathione