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

  • Authors:
    • Wentao Fu
    • Leying Lin
    • Jie Li
    • Fei Qin
    • Chuan Chen
    • Yinglian Cai
    • Yilun Cai
    • Yiling Huang
    • Wang Yang
    • Shanshan Zhu
  • View Affiliations / Copyright

    Affiliations: Department of Pharmacy, Xiamen Medical College, Xiamen, Fujian 361023, P.R. China, Department of Pharmacy, Innovation Research Center for Biological Enzyme Catalysis and Drug Synthesis, Xiamen Medical College, Xiamen, Fujian 361023, P.R. China, Department of Pharmacy, Xiamen Traditional Chinese Medicine Hospital, Xiamen, Fujian 361006, P.R. China
    Copyright: © Fu et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Article Number: 63
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    Published online on: February 2, 2026
       https://doi.org/10.3892/or.2026.9068
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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.

View Figures

Figure 1

Effects of Que on cell viability,
mRNA levels, apoptosis and protein expression in MCF-7 cells. (A)
Cell viability of MCF-7 cells treated with the indicated
concentrations of Que for 24 and 48 h, as determined by the Cell
Cycle Kit-8 assay. (B) mRNA expression levels of ABCB1, ABCC2 and
ABCG2 following Que treatment. (C) Representative western blotting
images, (D) protein expression levels of ABCB1, ABCC2 and ABCG2,
and (E) Bax, Bcl-2, and cleaved caspase-3 were assessed by western
blotting. (F) Representative images of flow cytometry and (G)
apoptosis rate was analyzed by flow cytometry after Annexin
V-FITC/PI staining. Data are presented as the mean ± SEM of at
least three independent experiments. Statistical significance was
determined by one/two-way ANOVA followed by Bonferroni's post hoc
test for multiple comparisons. *P<0.05, **P<0.01 compared
with the control group, ##P<0.01 compared with the
Que (24 h) group. Que, Quercetin; Ctrl, control.

Figure 2

Effects of PTEN overexpression in
MCF-7 cells. mRNA expression levels of (A) PTEN, (B) ABCB1, ABCC2,
ABCG2, Bax and Bcl-2 following PTEN overexpression. (C)
Representative western blotting images and protein expression
levels of (D) ABCB1, ABCC2, ABCG2, (E) PTEN, Bax and Bcl-2
following PTEN overexpression. The results are presented as the
mean ± SEM of at least three independent experiments and analyzed
using one-way ANOVA followed by Bonferroni's post hoc test.
*P<0.05, **P<0.01 compared with the Plvx-con group.

Figure 3

PTEN overexpression enhances the
effects of Que on MCF-7 cells. (A) Cell viability following
combined PTEN overexpression and Que (60 µM) treatment, as
determined by the CCK-8 assay. mRNA expression levels of (B) PTEN,
(C) Bax and Bcl-2 in different treatment groups. (D) Cell viability
assessed by Hoechst 33342 staining (scale bar, 100 µm). (E)
Representative western blotting images and (F) Protein expression
levels of PTEN, (G) Bax and (H) Bcl-2 in different treatment
groups. Data are presented as the mean ± SEM of at least three
independent experiments. Statistical significance was determined by
one/two-way ANOVA followed by Bonferroni's post hoc test for
multiple comparisons. *P<0.05, **P<0.01, ***P<0.001
compared with the 0 µmol/l Que group, ##P<0.01
compared with the Plvx-con group. Que, Quercetin; con, control.

Figure 4

Effects of combined PTEN
overexpression and Que treatment on ABC transporters and the
PI3K/AKT signaling pathway in MCF-7 cells. mRNA expression levels
of (A) ABCB1, (B) ABCC2 (C) and ABCG2 in different treatment
groups. (D) Representative images and (E) protein expression levels
of ABCB1, ABCC2, ABCG2, (F) p-PI3K, and (G) p-AKT were evaluated by
western blotting. The results are presented as the mean ± SEM of at
least three independent experiments and analyzed using one-way
ANOVA followed by Bonferroni's post hoc test. *P<0.05,
**P<0.01, ***P<0.001 compared with the Plvx-con group. Que,
Quercetin; con, control; p, phosphorylated.

Figure 5

Effects of combined LY294002 and Que
treatment on apoptosis and protein expression in MCF-7 cells. (A)
Representative western blotting images and Protein expression
levels of (B) ABCB1, ABCC2, ABCG2, (C) p-PI3K (D) PTEN, Bax, Bcl-2
and (E) p-AKT in different treatment groups. (F) mRNA expression
levels of ABCB1, ABCC2, ABCG2, PTEN, Bax and Bcl-2 in different
treatment groups. (G) Representative immunofluorescence images of
ABCG2 expression (green). Nuclei were counterstained with DAPI
(blue). Scale bar, 50 µm. (H) Representative flow cytometry images
and (I) Apoptosis rate was analyzed by flow cytometry after Annexin
V-FITC/PI staining. The results are presented as the mean ± SEM of
at least three independent experiments and analyzed using two-way
ANOVA followed by Bonferroni's post hoc test. *P<0.05,
**P<0.01 compared with the control group; ##P<0.05
compared with the Que group. Que, Quercetin; Ctrl, control; p,
phosphorylated.

Figure 6

Effects of combined LY294002 and Que
treatment on Rhodamine 123 accumulation in MCF-7 cells. (A)
Representative fluorescence images of intracellular Rhodamine 123
(green). Scale bar, 200 µm. (B) Quantitative analysis of Rhodamine
123 fluorescence intensity. The results are presented as the mean ±
SEM of at least three independent experiments and analyzed using
one-way ANOVA followed by Bonferroni's post hoc test. **P<0.01
compared with the control group. Que, Quercetin; Ctrl, control.
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Copy and paste a formatted citation
Spandidos Publications style
Fu W, Lin L, Li J, Qin F, Chen C, Cai Y, Cai Y, Huang Y, Yang W, Zhu S, Zhu S, et al: <p>Quercetin reduces expression of ATP‑binding cassette transporters by regulating the PTEN/PI3K/AKT signaling pathway in breast cancer cells</p>. Oncol Rep 55: 63, 2026.
APA
Fu, W., Lin, L., Li, J., Qin, F., Chen, C., Cai, Y. ... Zhu, S. (2026). <p>Quercetin reduces expression of ATP‑binding cassette transporters by regulating the PTEN/PI3K/AKT signaling pathway in breast cancer cells</p>. Oncology Reports, 55, 63. https://doi.org/10.3892/or.2026.9068
MLA
Fu, W., Lin, L., Li, J., Qin, F., Chen, C., Cai, Y., Cai, Y., Huang, Y., Yang, W., Zhu, S."<p>Quercetin reduces expression of ATP‑binding cassette transporters by regulating the PTEN/PI3K/AKT signaling pathway in breast cancer cells</p>". Oncology Reports 55.4 (2026): 63.
Chicago
Fu, W., Lin, L., Li, J., Qin, F., Chen, C., Cai, Y., Cai, Y., Huang, Y., Yang, W., Zhu, S."<p>Quercetin reduces expression of ATP‑binding cassette transporters by regulating the PTEN/PI3K/AKT signaling pathway in breast cancer cells</p>". Oncology Reports 55, no. 4 (2026): 63. https://doi.org/10.3892/or.2026.9068
Copy and paste a formatted citation
x
Spandidos Publications style
Fu W, Lin L, Li J, Qin F, Chen C, Cai Y, Cai Y, Huang Y, Yang W, Zhu S, Zhu S, et al: <p>Quercetin reduces expression of ATP‑binding cassette transporters by regulating the PTEN/PI3K/AKT signaling pathway in breast cancer cells</p>. Oncol Rep 55: 63, 2026.
APA
Fu, W., Lin, L., Li, J., Qin, F., Chen, C., Cai, Y. ... Zhu, S. (2026). <p>Quercetin reduces expression of ATP‑binding cassette transporters by regulating the PTEN/PI3K/AKT signaling pathway in breast cancer cells</p>. Oncology Reports, 55, 63. https://doi.org/10.3892/or.2026.9068
MLA
Fu, W., Lin, L., Li, J., Qin, F., Chen, C., Cai, Y., Cai, Y., Huang, Y., Yang, W., Zhu, S."<p>Quercetin reduces expression of ATP‑binding cassette transporters by regulating the PTEN/PI3K/AKT signaling pathway in breast cancer cells</p>". Oncology Reports 55.4 (2026): 63.
Chicago
Fu, W., Lin, L., Li, J., Qin, F., Chen, C., Cai, Y., Cai, Y., Huang, Y., Yang, W., Zhu, S."<p>Quercetin reduces expression of ATP‑binding cassette transporters by regulating the PTEN/PI3K/AKT signaling pathway in breast cancer cells</p>". Oncology Reports 55, no. 4 (2026): 63. https://doi.org/10.3892/or.2026.9068
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