期刊
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
卷 219, 期 -, 页码 1122-1134出版社
ELSEVIER
DOI: 10.1016/j.ijbiomac.2022.08.150
关键词
Affitoxin; Diphtheria toxin; Affibody; HER3; Flow cytometry
资金
- Avicenna Research Insti- tute [960205-014]
In this study, a new affitoxin was designed and tested for its ability to target and kill HER3 positive breast cancer cells. The results showed that the affitoxin specifically bound to HER3 positive cells and had the potential to be a new treatment option for HER3-positive cancers.
High expression of receptor tyrosine-protein kinase erbB-3 (HER3) has been found in several malignancies such as breast cancer. In this study, we designed, produced and evaluated a new affitoxin consisting of a truncated form of diphtheria toxin and a HER3-binding affibody domains. The new affitoxin was expressed in Escherichia coli and purified by affinity chromatography. We evaluated the suitability of affitoxin to kill HER3 positive breast cancer cells with MTT and apoptosis assays. The protein synthesis inhibition was also evaluated. The IC50 value in HER3 negative cells is about 10 times more than HER3 positive cells in new design of affitoxin. The specificity of affitoxin for binding to HER3 positive cells was also investigated with binding assay with flow cytometry. The results show that, the new affitoxin is an anti-cancer molecule with specific binding to HER3 positive cells and may open a new window for the treatment of HER3-positive cancers.
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