Inhibition of Erbb2 by Trastuzumab Induces Oxidative Stress Markers in HER2 Positive Breast Cancer Cell Lines

• Main Authors: Zahra Mohammadi Abgarmi, Abbas Sahebghadam Lotfi, Saeid Abroun, Masoud Soleimani, Shahla Moahammad Ganji
• Format: Article
• Language: English
• Published: Amber Publication 2018-03-01
• Series: Journal of Research in Medical and Dental Science
• Subjects: Trastuzumab; HER2 Positive Breast Cancer; Reactive Oxygen Species; Malondialdehyde
• Online Access: https://www.jrmds.in/articles/inhibition-of-erbb2-by-trastuzumab-induces-oxidative-stress-markers-in-her2-positive-breast-cancer-cell-lines.pdf

Human epidermal growth factor receptor2 (HER2) amplification occurs in approximately 30% of breast cancers that associated with a faster rate of growth and a poorer prognosis. Trastuzumab is FDA-approved humanized monocholonal antibody that targets the extracellular domain of HER2. In present study we blocked HER2 signaling pathways with trastuzumab and assessed oxidative stress markers in breast cancer cell lines. After MTT test, IC50 of trastuzumab on breast cancer cells were calculated with CompuSyn software. Cells treated with various concentration of trastuzumab. Intracellular ROS determined with DCFH-DA fluorimetric probe, MDA as lipid peroxidation index detected with TBARS method. Protein carbonyl contents of cells were assessed with DNPH derivatization spectrophotometrically at 360-385 nm. Our results showed that trastuzumab treatment increases reactive oxygen species, lipid peroxidation and protein carbonyl content in HER2 positive breast cancer cell lines. These results provide evidence that increasing of oxidative stress markers in HER2 overexpressing compared to HER2 negative breast cancer cell lines after treatment with trastuzumab can be exploited for selective HER2 positive cancer cells therapy; combination of trastuzumab with ROS producing agents renders them more susceptible and induces cell death