چاپ صفحه |  صفحه نخست سامانه |  نویسندگان |  اطلاعات تفضیلی |  دانلود مقاله | دانشگاه علوم پزشکی تبریز |
| نویسنده | نفر چندم مقاله |
|---|---|
| مصطفی اکبرزاده خیاوی | اول |
| اعظم صفری | دوم |
| سید کاظم میری نژاد | سوم |
| محمد حسین صومی | چهارم |
| عنوان | متن |
|---|---|
| خلاصه مقاله | Introduction The receptor for an epidermal growth factor (EGFR) is an attractive target for cancer immunotherapy, as it is a tyrosine kinase receptor overexpressed on tumor cells with a key role in the development of malignancy. Cetuximab (Cet) is an EGFR inhibitor medication used for metastatic colorectal cancer (CRC); however, its therapeutic efficacy is limited due to resistance mechanisms in some patients. The current study aimed to provide a novel immune-RNase based on the conjugation of Cet with RNase enzyme as an anti-EGFR biosystem against CRC. Materials and Methods A novel immuno-RNase, called anti-EGFR antibody-RNase A (Cet-RNaseA), is produced from the conjugation of anti-EGFR antibody Cet and bovine pancreatic RNase (RNase A). After synthesizing Cet-RNaseA, the physicochemical properties of Cet-RNaseA were characterized by SDS-PAGE, BCA kit, and UV-vis spectrum. Furthermore, its biological impacts, including cell viability, apoptosis, and ERK1, ERK2, Bax, and Bcl2 gene expression, were evaluated in the KRAS mutant SW-480 cells. Results Cet-RNaseA retained the enzymatic activity of RNase A and was specifically bound to EGFR-positive cells with an affinity comparable with the free RNase A and Cet. In addition, the maximum anti-apoptosis effect was obtained after treating cells with an IC50 dose of Cet-RNase A compared to free RNase A and Cet. Based on real-time PCR data, in the treated KRAS mutant SW-480 cells with the Cet-RNase A, the expression level of Bax, ERK1, and ERK2 were significantly increased, while the expression of Bcl2 was significantly decreased compared to the untreated control cells. Conclusion The novel immune-RNase showed an effective and targeted antiproliferative activity against EGFR-positive CRC cells, which was more potent than the free RNase A and Cet alone. In conclusion, Cet-RNase A could be considered a promising candidate for the immunotherapy of EGFR-positive tumors. |
| کلمات کلیدی | Colorectal cancer, EGFR, Cetuximab, ImmunoRNase |
| نام فایل | تاریخ درج فایل | اندازه فایل | دانلود |
|---|---|---|---|
| 1.pdf | 1401/10/28 | 990916 | دانلود |
| certificate.pdf | 1401/10/28 | 137259 | دانلود |
