TY - JOUR ID - 47153 TI - Specific Targeting of Recombinant Human Pancreatic Ribonuclease 1 using Gonadotropin-Releasing Hormone Targeting Peptide toward Gonadotropin-Releasing Hormone Receptor-Positive Cancer Cells JO - Iranian Journal of Medical Sciences JA - IJMS LA - en SN - 0253-0716 AU - Maleksabet, Amir AU - Zarei Jaliani, Hossein AU - Asgari, Amir AU - Ramezani, Amin AU - Erfani, Nasrollah AD - Department of Medical Biotechnology, School of Advanced Medical Sciences and Technologies, Shiraz University of Medical Sciences, Shiraz, Iran AD - Department of Medical Biotechnology, School of Medicine, Shahid Sadoughi University of Medical Sciences, Yazd, Iran AD - School of Pharmacy and Pharmaceutical Sciences, University of Alberta, Edmonton, AB, Canada AD - Shiraz Institute for Cancer Research, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran Y1 - 2021 PY - 2021 VL - 46 IS - 4 SP - 281 EP - 290 KW - Drug delivery systems KW - Ribonucleases KW - Pancreatic KW - Gonadotropin-releasing hormone DO - 10.30476/ijms.2020.83234.1219 N2 - Background: Targeted drug delivery is a novel method to specifically deliver anticancer therapeutics to tumor sites. Gonadotropin-releasing hormone (GnRH) is a decapeptide, and its target binding property has attracted attention as a means of targeted drug delivery. Human pancreatic ribonuclease 1 (hpRNase1) has been shown to exert anticancer properties, when fused to a targeting moiety. The goal of the present study was to add a GnRH targeting peptide to the N-terminus of hpRNase1 to specifically target GnRH receptor (GnRH-R) expressing cells. Methods: This in vitro study was conducted at Shiraz Institute for Cancer Research (Shiraz, Iran) in 2019. The coding sequence of GnRH and hpRNase1 were fused, and the chimeric protein together with non-fused hpRNase1 were produced in E. coli (BL21). The recombinant proteins were purified, and their biological activity was evaluated using MTT and apoptosis assays. Non-parametric Kruskal–Wallis tests with Dunn’s post hoc tests were performed to determine the significant differences between the study groups.Results: GnRH-hpRNase1 chimeric protein specifically inhibited the proliferation of PC-3 (P=0.021), LNCaP (P=0.034), and AD-Gn (P=0.041) cells, while the growth of negative cells (AD-293) was not significantly affected (P=0.081). GnRH-hpRNase1 decreased the IC50 values more than non-fused hpRNase1, by approximately 26.5-fold (P=0.036) for PC-3 cells, and exerted its growth inhibitory effects through apoptosis induction. Conclusion: Fusion of GnRH to hpRNase1 structure produced an enzyme, which could specifically target tumor cells. This approach can be used to eliminate tumors that harbor GnRH-R. UR - https://ijms.sums.ac.ir/article_47153.html L1 - https://ijms.sums.ac.ir/article_47153_9de8e09828562e26162e11c6fb5e84c2.pdf ER -