Improvement of Targeted Chemotherapy of HER۲-positive Ovarian Malignant Cell Line by ZHER۲-Idarubicin Conjugate: An in vitro Study

Background & objectives: Overexpression of human epidermal growth factor receptor ۲ (HER۲) causes cell transformation and development of various types of malignancies. Idarubicin is an effective anti-neoplastic drug but specific delivery of it 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 HER۲ receptors. Breast and ovarian cancers as wide speared types of malignancies are associated with high expression of HER۲. In the current study, we assessed the cytotoxic effects of idarubicin-ZHER۲ affibody conjugate on the positive-HER۲ cancer cell lines.  Methods: The cytotoxic effects of constructed idarubicin-ZHER۲ affibody conjugate on the SK-BR-۳, SK-OV-۳, and MCF-۷ cells with various levels of HER۲ expression were evaluated by MTT assay after ۴۸ hours of incubation time. Results: Idarubicin showed a potent and dose-dependent cytotoxic effect against all treated cell lines while the SK-OV-۳ cells were significantly more sensitive. The dimeric form of the ZHER۲ affibody molecule showed a mild effect on the cell viability of all treated cells at its optimum concentration. The constructed Idarubicin-ZHER۲ affibody conjugate decreased the viability of SK-OV-۳ cells at its optimal concentration, more efficiently and specifically than other treated cells.  Conclusion: The ZHER۲-affibody conjugate of idarubicin has a more specific cytotoxic effect compared with idarubicin alone against HER۲-overexpressing ovarian cancerous cells. It appears the ZHER۲-affibody conjugate of idarubicin has great potential to be implicated as an innovative anti-cancer agent in future clinical trials in patients with HER۲-overexpressing ovarian cancer.

Keywords:

Idarubicin , ZHER۲ affibody , idarubicin-ZHER۲ affibody conjugate , Ovarian Cancer