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Updated: Apr 18, 2026

Monitoring of Nanodrug Accumulation in Murine Breast Cancer Metastases
Published on: August 23, 2024
[miR-34a may regulate sensitivity of breast cancer cells to adriamycin via targeting Notch1]
Xiujuan Li1, Jianhua Zhao, Jinhai Tang2
1Department of General Surgery, Jiangsu Cancer Hospital, Nanjing 210009, China.
Objective:
To explore the influence of miR-34a on Notch1 expression in breast cancer cells, and to explore the role of miR-34a in the sensitivity of breast cancer cells to Adriamycin (ADR).
Methods:
The expression of miR-34a in MCF-7 and MCF-7/ADR cells were detected by real-time fluorescence quantitative PCR. Cells were transfected with miR-34a mimics or inhibitor using Lipofectamine 2000. Expression of Notch1 in the two groups before and after transfection was detected by real-time fluorescence quantitative PCR and Western blot. MTT test and apoptosis assay were performed to observe the impact of miR-34a expression on the sensitivity of breast cancer cells to ADR. Statistical analysis of the results was conducted using SPSS 16.0 software. The experiment was repeated independently for at least three times, and had a good reproducibility. The data were shown as mean ± standard deviation. The analysis of variance between groups used one-way ANOVA test. Correlation between groups was analyzed using Spearman rank test. P < 0.05 was considered statistically significant.
Results:
Compared with the control MCF-7 cells, the relative expression level of miR-34a in MCF-7/ADR cells was significantly decreased to 0.02 (P < 0.05). In the MCF-7 ADR-resistant cells, Notch1 mRNA expression was increased compared with that in the MCF-7 ADR-sensitive cells (2.10 ± 0.20-fold, P < 0.05). The expression levels of Notch1 mRNA and protein in MCF-7/ADR cells transfected with miR-34a mimics were significantly up-regulated. On the contrary, the expressions of Notch1 mRNA and protein in MCF-7 cells transfected with miR-34a inhibitor were down-regulated. The IC50 value of ADR in the control MCF-7/ADR cells and cells transfected with miR-34a mimics was (116.33 ± 16.80) and (39.28 ± 4.12) µmol/L, respectively (P < 0.05). The IC50 value of ADR in control MCF-7 cells and cells transfected with miR-34a inhibitor was (0.29 ± 0.21) and (0.51 ± 0.03) µmol/L, respectively (P < 0.05). Further, overexpression of miR-34a significantly enhanced apoptosis in the ADR-treated MCF-7/ADR cells, and miR-34a inhibitor reduced apoptosis in the ADR-treated MCF-7 cells.
Conclusions:
miR-34a negatively regulates the expression of Notch1 at both mRNA and protein levels. Overexpression of miR-34a may sensitize MCF-7/ADR cells to adriamycin.
Insights
MicroRNA-34a (miR-34a) negatively regulates Notch1 expression in breast cancer cells. Increasing miR-34a may enhance the sensitivity of Adriamycin-resistant breast cancer cells to chemotherapy.
Area of Science:
- Molecular Biology
- Oncology
- Biochemistry
Background:
- MicroRNAs (miRNAs) play crucial roles in gene regulation and are implicated in various diseases, including cancer.
- Notch signaling is a conserved pathway involved in cell differentiation, proliferation, and survival, and its dysregulation is linked to cancer development.
- Adriamycin (ADR) is a widely used chemotherapy drug, but resistance can limit its efficacy in treating breast cancer.
Purpose of the Study:
- To investigate the regulatory relationship between miR-34a and Notch1 in breast cancer cells.
- To determine the impact of miR-34a on the sensitivity of breast cancer cells to Adriamycin (ADR).
Main Methods:
- Quantitative real-time PCR and Western blot were used to measure miR-34a and Notch1 expression.
- MCF-7 and MCF-7/ADR cells were transfected with miR-34a mimics or inhibitors.
- Cell viability (MTT assay) and apoptosis assays were performed to assess ADR sensitivity.
- Statistical analyses included ANOVA and Spearman rank correlation.
Main Results:
- miR-34a expression was significantly decreased in Adriamycin-resistant MCF-7/ADR cells compared to sensitive MCF-7 cells.
- Notch1 mRNA and protein levels were elevated in MCF-7/ADR cells and inversely correlated with miR-34a levels.
- Overexpression of miR-34a in MCF-7/ADR cells reduced ADR IC50 values and enhanced apoptosis.
- Inhibition of miR-34a in MCF-7 cells increased ADR IC50 values and reduced apoptosis.
Conclusions:
- miR-34a acts as a negative regulator of Notch1 expression at both mRNA and protein levels in breast cancer cells.
- Restoring miR-34a levels can potentially overcome Adriamycin resistance in breast cancer by sensitizing cells to the drug.
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