Resistance to chemotherapy drugs, such as adriamycin (ADR), is a common problem in acute myeloid leukemia (AML) patients. We hypothesized that the natural compound resveratrol (Res) may reverse AML drug resistance through the PI3K/Akt/Nrf2 pathway. We investigated the in vitro effect of Res using human promyelocytic leukemia cells (HL-60) and the ADR-resistant cell line (HL-60/ADR) and treated with either Res or ADR+Res. Cellular proliferation inhibition rate, auto-fluorescence intensity of ADR in HL-60/ADR cells and HL-60 cells, mRNA expression of Nrf2 and the drug-resistant gene MRP1, and protein expression of PI3K, Akt, p-Akt, Nrf2, and MRP1 were measured. Results showed ADR+Res had a more significant inhibitory effect than ADR alone on HL-60/ADR cells. Auto-fluorescence intensity of ADR in HL-60/ADR cells treated with ADR+Res significantly increased. No difference of the auto-fluorescence intensity of ADR was observed in HL-60 cells treated with ADR and ADR+Res. mRNA expression of Nrf2 and MRP1 significantly decreased in HL-60/ADR cells treated with both Res and ADR+Res; protein expression of PI3K, p-Akt, Nrf2, and MRP1 significantly decreased in HL-60/ADR cells treated with PI3K inhibitor, Res and ADR+Res. In conclusion, Res reverses the drug resistance of AML HL-60/ADR cells through regulation of the PI3K/Akt/Nrf2 signaling pathway and MRP1 expression.
基金：
Project of Science and Technology, Department of Hebei Province [16277734D]; Medical Science Research Foundation of Hebei Province Health Bureau, China [20130159, 20130176]
第一作者机构：[1]Hebei Med Univ, Dept Clin Lab, Hosp 2, Shijiazhuang 050000, Hebei, Peoples R China
通讯作者：
通讯机构：[1]Hebei Med Univ, Dept Clin Lab, Hosp 2, Shijiazhuang 050000, Hebei, Peoples R China[3]Oregon Hlth & Sci Univ, Div Hematol Oncol, Knight Canc Inst, Portland, OR 97239 USA[*1]Department of Clinical Laboratory, The Second Hospital of Hebei Medical University, Shijiazhuang, Hebei 050000, China[*2]Oregon Health & Science University, 3181 SW Sam Jackson Park Road, Portland, Oregon 97239, USA.
推荐引用方式(GB/T 7714)：
Li Yongjun,Guo Yukai,Feng Zhuang,et al.Involvement of the PI3K/Akt/Nrf2 Signaling Pathway in Resveratrol-Mediated Reversal of Drug Resistance in HL-60/ADR Cells[J].NUTRITION AND CANCER-AN INTERNATIONAL JOURNAL.2019,71(6):1007-1018.doi:10.1080/01635581.2019.1578387.
APA：
Li, Yongjun,Guo, Yukai,Feng, Zhuang,Bergan, Raymond,Li, Bo...&Shi, Min.(2019).Involvement of the PI3K/Akt/Nrf2 Signaling Pathway in Resveratrol-Mediated Reversal of Drug Resistance in HL-60/ADR Cells.NUTRITION AND CANCER-AN INTERNATIONAL JOURNAL,71,(6)
MLA：
Li, Yongjun,et al."Involvement of the PI3K/Akt/Nrf2 Signaling Pathway in Resveratrol-Mediated Reversal of Drug Resistance in HL-60/ADR Cells".NUTRITION AND CANCER-AN INTERNATIONAL JOURNAL 71..6(2019):1007-1018
