Investigating the Cytotoxic and Anti-proliferative Effects of Trastuzumab on MDA-MB-453 and MDA-MB-468 Breast Cell Lines With Different Levels of HER2 Expression

Introduction: Trastuzumab is a common treatment for HER2-positive breast cancer. Trastuzumab exerts its effect through inhibiting the intracellular signaling pathway induced by HER2. This study aimed to specifically investigate the cytotoxic effect of trastuzumab against two different breast cell lines, MDA-MB-453 (HER2-high) and MDA-MB-468 (HER2-low). Materials and Methods: The breast cancer cell lines were subjected to various concentrations of trastuzumab (1-1000 ng/mL). The trastuzumab’s effects were regularly monitored via direct observation by inverted microscopy. Effects of trastuzumab were determined on cytotoxicity, cell proliferation and apoptosis at 24 and 72 hours post-treatment via MTT colorimetric, cell cycle and apoptosis assays. Results: Microscopic observation demonstrated a dose-dependent increase in cell death at treated ones. The MTT assay showed that trastuzumab (1-1000 ng/mL) inhibited the growth of both cell lines in a dose-dependent manner. The findings of the present study revealed that trastuzumab induces a statistically higher cytotoxicity at all concentrations in MDA-MB-453 compared to MDA-MB-468 cells. It has been actually revealed that trastuzumab suppresses cell proliferation through inducing G1 phase arrest and triggers apoptosis in both cell lines. However, the effect of trastuzumab was found to be higher in MDA-MB-453, compared to MDA-MB-468. Conclusions: Trastuzumab could inhibit cell proliferation and trigger apoptosis in HER2-positive cells. Although Trastuzumab affected both cell lines, it significantly inhibited the cell growth of HER2-high cells.

Keywords:

Trastuzumab , MDA-MB-453 , breast cancer , MDA-MB-468 , Cytotoxicity , Apoptosis