• Specific Targeting of Recombinant Human Pancreatic Ribonuclease 1 using Gonadotropin-Releasing Hormone Targeting Peptide toward Gonadotropin-Releasing Hormone Receptor-Positive Cancer Cells
  • Amir Maleksabet,1,* Negar Meschi,2 Sarvenaz Janbaz,3
    1. Mazandaran University of Medical Sciences
    2. Mazandaran University of Medical Sciences
    3. Mazandaran University of Medical Sciences


  • Introduction: Targeted drug delivery is a novel method to deliver anticancer therapeutics to tumor sites specifically. 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 target GnRH receptor (GnRH-R) expressing cells specifically.
  • Methods: The coding sequence of GnRH and hpRNase1 were fused, and the chimeric protein together with non-fused hpRNase1 was 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, which harbor GnRH-R.
  • Keywords: Drug delivery systems, Ribonucleases, Pancreatic, Gonadotropin-releasing hormone