Involvement of the PI3K/Akt/Nrf2 Signaling Pathway in Resveratrol-Mediated Reversal of Drug Resistance in HL-60/ADR Cells

Yongjun Li, Yukai Guo, Zhuang Feng, Raymond Bergan, Bo Li, Yongliang Qin, Lianmei Zhao, Zhenzhen Zhang, Min Shi

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Abstract

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.

Original languageEnglish (US)
JournalNutrition and Cancer
DOIs
Publication statusPublished - Jan 1 2019

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ASJC Scopus subject areas

  • Medicine (miscellaneous)
  • Oncology
  • Nutrition and Dietetics
  • Cancer Research

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