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Trastuzumab Induces Apoptosis and Cell Cycle Arrest in Triple-Negative Breast Cancer, Suggesting Repurposing
Shaimaa Abdel-Ghany1, Yasmin Khalid1, Soha Mohamed1
1Department of Environmental Biotechnology, College of Biotechnology, Misr University for Science & Technology, Giza, Egypt.
Background:
Breast cancer remains the most common invasive cancer in women worldwide. Triple-negative breast cancer (TNBC) is an aggressive subtype with limited treatment options. Trastuzumab (Tz) is typically used to treat HER2-positive breast cancers, but its potential in TNBC is unclear.
Objectives:
To investigate the effects of trastuzumab on cell viability, apoptosis, cell cycle progression, and gene expression in TNBC cell lines compared with HER2-positive and normal cell lines.
Design:
This is an in vitro experimental pre-clinical study using cultured cancer cell lines.
Methods:
MDA-MB-231 and 4T1 (TNBC), MCF-7 (HER2-positive), and HSF (normal) cell lines were treated with 20 μg/mL trastuzumab for 24 hours. Cell viability was assessed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, apoptosis by flow cytometry, cell cycle progression by DNA content analysis, and gene expression by qPCR.
Results:
Trastuzumab significantly reduced cell viability and induced apoptosis in TNBC cell lines, comparable to effects in HER2-positive MCF-7 cells. Cell cycle analysis revealed G2/M phase arrest in TNBC cells. Gene expression analysis showed upregulation of ERBB2, NOTCH1, EGFR, PIK3CA, and PTEN in MDA-MB-231 cells, while 4T1 cells exhibited downregulation of most genes except NOTCH1.
Conclusion:
This study provides initial evidence for trastuzumab's potential therapeutic effects in TNBC, despite low HER2 expression. The observed cytotoxicity, apoptosis induction, and cell cycle modulation in TNBC cells warrant further investigation into trastuzumab's mechanisms of action in HER2-negative contexts and its potential repurposing for TNBC treatment.
Insights
Trastuzumab shows potential against triple-negative breast cancer (TNBC) by reducing cell viability and inducing apoptosis. Further research is needed to explore its mechanisms in HER2-negative contexts for TNBC treatment.
Area of Science:
- Oncology
- Molecular Biology
- Pharmacology
Background:
- Breast cancer is a leading cause of cancer death in women globally.
- Triple-negative breast cancer (TNBC) is an aggressive subtype with limited therapeutic options.
- Trastuzumab (Tz) is a targeted therapy for HER2-positive breast cancer, but its efficacy in TNBC is not well-established.
Purpose of the Study:
- To evaluate the in vitro effects of trastuzumab on TNBC cell lines.
- To compare these effects with those on HER2-positive and normal cell lines.
- To investigate trastuzumab's impact on cell viability, apoptosis, cell cycle, and gene expression in TNBC.
Main Methods:
- Utilized TNBC (MDA-MB-231, 4T1), HER2-positive (MCF-7), and normal (HSF) cell lines.
- Treated cells with 20 μg/mL trastuzumab for 24 hours.
- Assessed cell viability (MTT assay), apoptosis (flow cytometry), cell cycle (DNA content), and gene expression (qPCR).
Main Results:
- Trastuzumab significantly decreased cell viability and induced apoptosis in TNBC cells, similar to effects in HER2-positive cells.
- Cell cycle analysis indicated G2/M phase arrest in TNBC cells treated with trastuzumab.
- Gene expression profiling revealed varied responses in TNBC cell lines, with upregulation of key genes like ERBB2 and NOTCH1 in MDA-MB-231 cells.
Conclusions:
- Trastuzumab demonstrates potential therapeutic activity against TNBC cells in vitro, irrespective of HER2 expression levels.
- The findings suggest trastuzumab may induce cytotoxicity, apoptosis, and cell cycle modulation in TNBC.
- Further investigation into trastuzumab's mechanisms in HER2-negative settings is warranted for potential TNBC repurposing.
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