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.

Abstract

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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