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The tissue transglutaminase: a potential target regulating MDR in breast cancer
Objective:
Multi-drug resistance (MDR) is the main obstacle influencing the anti-tumor effect in breast cancer. To date, no proper potential targets are found to overcome MDR. Here, tTG was explored to show whether it is a potential target to regulate MDR in breast cancer.
Materials And Methods:
tTG was silenced by small interfere siRNA. After that, the mRNA level of CD44, CD24, LRP, MRP and MDR1 were detected by RT-PCR. The Western blot analysis was used to detect the expression of LRP, P-gp and MRP. In addition, the impact of tTG on cell apoptosis, as well as cell proliferation were observed. Finally, to evaluate the role of tTG in BALB/c nude mice, the growth of tumor was performed, and the immunohistochemistry analysis was used to observe the expression of LRP, P-gp and MRP in vivo.
Results:
In MCF-7/ADR, Compared to MCF-7, tTG expression was highly increased. After silencing tTG, the mRNA level and the protein level of P-gp, MRP, LRP were both differently decreased. The mRNA level of CD44 and CD24 was also down-regulated after silencing tTG. In addition, the cell proliferation was significantly inhibited in the ADR + tTG siRNA+Adriamycin group (p<0.05), and the tumor growth was prevented in a time-dependent situation. Cell apoptosis was significantly strengthened in the ADR+tTG siRNA+Adriamycin group (p<0.05). In vivo, the growth of tumors was reduced after silencing tTG, and the LRP, P-gp and MRP expression were significantly down-regulated in ADR + tTG SiRNA +adriamycin group (p<0.05).
Conclusions:
It is concluded that the tTG may be a potential target regulating the MDR by regulating LRP, P-gp and MRP expression as well as the expression of CD44CD24 to improve the MDR in breast cancer.
Insights
Transglutaminase 2 (tTG) may be a new target to overcome multi-drug resistance (MDR) in breast cancer. Silencing tTG reduced tumor growth and MDR markers, improving treatment efficacy.
Area of Science:
- Oncology
- Molecular Biology
- Biochemistry
Background:
- Multi-drug resistance (MDR) is a major challenge in breast cancer therapy.
- Identifying novel targets to overcome MDR is crucial for improving anti-tumor effects.
Purpose of the Study:
- To investigate the potential of transglutaminase 2 (tTG) as a target for overcoming MDR in breast cancer.
- To explore the role of tTG in regulating key MDR-associated genes and proteins.
Main Methods:
- Silencing tTG using small interfering RNA (siRNA).
- Quantification of mRNA levels for CD44, CD24, LRP, MRP, and MDR1 via RT-PCR.
- Western blot analysis for LRP, P-gp, and MRP protein expression.
- Assessment of cell apoptosis and proliferation in vitro.
- In vivo tumor growth studies in BALB/c nude mice with immunohistochemistry analysis.
Main Results:
- tTG expression was significantly higher in drug-resistant MCF-7/ADR cells compared to MCF-7 cells.
- Silencing tTG led to decreased mRNA and protein levels of LRP, P-gp, and MRP.
- Down-regulation of CD44 and CD24 mRNA was observed after tTG silencing.
- tTG silencing inhibited cell proliferation and tumor growth, while enhancing apoptosis.
- In vivo studies confirmed reduced tumor growth and down-regulated LRP, P-gp, and MRP expression upon tTG silencing.
Conclusions:
- tTG plays a significant role in regulating MDR in breast cancer.
- tTG is a potential therapeutic target for overcoming MDR by modulating LRP, P-gp, MRP, CD44, and CD24 expression.
- Targeting tTG may improve the efficacy of breast cancer treatment.
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