مشخصات پژوهش

صفحه نخست /The Enhanced Cytotoxic ...
عنوان
The Enhanced Cytotoxic Effects of the p28-Apoptin Chimeric Protein As A Novel Anti-Cancer Agent on Breast Cancer Cell Lines
نوع پژوهش مقاله چاپ شده
کلیدواژه‌ها
Selective tumor targeting, p28 peptide, Apoptin, Breast cancer
چکیده
Backgrounds Peptide-based drugs have shown promising results in overcoming the limitations of chemotherapeutic drugs by providing a targeted therapy approach to cancer. However, the response rate of targeted therapies is limited, in large part due to the intra- and inter-heterogeneity of tumors. Methods In this study, we engineered a novel chimeric protein composed of the p28 peptide as a tumor-homing killer peptide and apoptin as a killer peptide. We evaluated its cytotoxicity against MCF7 and MDA-MB-231 breast cancer cells and HEK-293 normal cells by the MTT assay. Different linkers were evaluated when designing the chimeric protein. Three-dimensional structure predictions of chimeric proteins with different linkers were carried out by Modeller 9.19, and their validation and analysis were performed by RAMPAGE. Results Results showed that a cleavable linker, including furin cleavage sites, is preferred over other linkers. The chimeric protein was then successfully expressed in E. coli and purifed by afnity chromatography under native conditions, then confrmed by SDS-PAGE and Western blot analysis. Compared with apoptin alone, the chimeric protein showed signifcantly higher toxicity against breast cancer cell lines in a dose-dependent manner. The IC50 values of the chimeric protein for MCF7 and MDA-MB-231 cells were 38.55 µg/mL and 43.11 µg/mL, respectively. There was no signifcant cytotoxic effect on the normal HEK293 cell line. Conclusion This study demonstrates that fusion of p28 peptide to a potent protein could provide an effective method for tumor targeting. Further, in vitro and in vivo studies of this novel chimeric protein are underway.
پژوهشگران احمد نوعی (نفر اول)، امیر نیلی احمد آبادی (نفر دوم)، میثم سلیمانی بدیع (نفر سوم)