Quercetin reduces expression of ATP‑binding cassette transporters by regulating the PTEN/PI3K/AKT signaling pathway in breast cancer cells

Oncol Rep. 2026 Apr;55(4):63. doi: 10.3892/or.2026.9068. Epub 2026 Feb 6.

Abstract

Breast cancer is a global health challenge for women and chemoresistance is a major contributor to its high mortality rates. Quercetin (Que), a flavonoid with antioxidant, antiviral, anti‑tumor and anti‑inflammatory properties, sensitizes cancer cells to chemotherapy. The present study investigated the mechanism by which Que regulates ATP‑binding cassette (ABC) transporter expression in MCF‑7 cells using a PTEN overexpression plasmid and the PI3K inhibitor LY294002. The present study assessed cell viability via Cell Counting Kit‑8 and Hoechst 33342 staining and analyzed mRNA and protein expression levels by reverse transcription‑quantitative PCR and western blotting. Apoptosis was evaluated by flow cytometry and ABCG2 expression was detected by immunofluorescence. Furthermore, the present study determined the effect of Que on drug uptake using a Rhodamine 123 accumulation assay. The results of the present study demonstrated that Que suppresses cell viability and induces apoptosis in MCF‑7 cells. Moreover, it enhances intracellular drug accumulation and downregulates ABC transporter expression by modulating the PTEN/PI3K/AKT signaling pathway.

Keywords: ATP‑binding cassette transporters; MCF‑7 cells; PTEN/PI3K/AKT pathway; apoptosis; breast cancer; drug uptake; quercetin.

MeSH terms

  • ATP Binding Cassette Transporter, Subfamily G, Member 2* / genetics
  • ATP Binding Cassette Transporter, Subfamily G, Member 2* / metabolism
  • ATP-Binding Cassette Transporters* / metabolism
  • Apoptosis / drug effects
  • Breast Neoplasms* / drug therapy
  • Breast Neoplasms* / genetics
  • Breast Neoplasms* / metabolism
  • Breast Neoplasms* / pathology
  • Cell Proliferation / drug effects
  • Cell Survival / drug effects
  • Drug Resistance, Neoplasm / drug effects
  • Female
  • Gene Expression Regulation, Neoplastic / drug effects
  • Humans
  • MCF-7 Cells
  • Neoplasm Proteins* / genetics
  • Neoplasm Proteins* / metabolism
  • PTEN Phosphohydrolase / genetics
  • PTEN Phosphohydrolase / metabolism
  • Phosphatidylinositol 3-Kinases / metabolism
  • Proto-Oncogene Proteins c-akt / metabolism
  • Quercetin* / pharmacology
  • Quercetin* / therapeutic use
  • Signal Transduction / drug effects

Substances

  • Quercetin
  • PTEN Phosphohydrolase
  • Proto-Oncogene Proteins c-akt
  • PTEN protein, human
  • Phosphatidylinositol 3-Kinases
  • ATP Binding Cassette Transporter, Subfamily G, Member 2
  • ABCG2 protein, human
  • ATP-Binding Cassette Transporters
  • Neoplasm Proteins