Improvement of Targeted Chemotherapy of HER2-positive Ovarian Malignant Cell Line by ZHER2-Idarubicin Conjugate: An in vitro Study

• Published in: Iranian journal of pathology Vol. 16; no. 2; pp. 109 - 118
• Main Authors: Siavoshinia, Leila, Jamalan, Mostafa, Zeinali, Majid, Pourshohod, Aminollah, Koushki, Mahdie, Moradipoodeh, Bahman, Mohammadzadeh, Ghorban
• Format: Journal Article
• Language: English
• Published: Tehran, Iran Iranian Society of Pathology 2021
• Subjects: idarubicin; idarubicin-zher2 affibody conjugate; Original; ovarian cancer; zher2 affibody
• ISSN: 1735-5303; 2345-3656
• DOI: 10.30699/IJP.2020.120392.2310

BACKGROUND & OBJECTIVEOverexpression of human epidermal growth factor receptor 2 (HER2) causes cell transformation and development of various types of malignancies. Idarubicin is an effective anti-neoplastic drug but its specific delivery to the targeted cells is still a great challenge. Affibody as a cost-effective peptide molecule with low molecular weight has a high affinity for HER2 receptors. Breast and ovarian cancers as wide speared types of malignancies are associated with high expression of HER2. In the current study, we assessed the cytotoxic effects of idarubicin-ZHER2 affibody conjugate on the positive-HER2 cancer cell lines. METHODSThe cytotoxic effects of constructed idarubicin-ZHER2 affibody conjugate on the SK-BR-3, SK-OV-3, and MCF-7 cells with various levels of HER2 expression were evaluated by MTT assay following 48 hours of incubation. RESULTSIdarubicin showed a potent and dose-dependent cytotoxic effect against all treated cell lines while the SK-OV-3 cells were significantly more sensitive. The dimeric form of the ZHER2 affibody molecule showed a mild effect on the cell viability of all treated cells at its optimum concentration. The constructed Idarubicin-ZHER2 affibody conjugate decreased the viability of SK-OV-3 cells at its optimal concentration, more efficiently and specifically than other treated cells. CONCLUSIONThe ZHER2-affibody conjugate of idarubicin has a more specific cytotoxic effect compared with idarubicin alone against HER2-overexpressing ovarian cancerous cells. It appears the ZHER2-affibody conjugate of idarubicin has great potential to be implicated as an innovative anti-cancer agent in future clinical trials in patients with HER2-overexpressing ovarian cancer.