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Updated: Jun 6, 2026
An Orthotopic Resectional Mouse Model of Pancreatic Cancer
Published on: September 24, 2020
Application of human pancreatic carcinoid BON cells for receptor-targeted drug development
Lichun Sun1, Lynsie M Morris, Jing Luo
1Department of Medicine, Peptide Research Laboratories, Tulane Health Sciences Center, New Orleans, LA 70112-2699, USA. lsun@tulane.edu
Abstract:
In our previous study, we found that several tumor cell lines displayed high receptor-specific binding affinity, one of which, the human pancreatic carcinoid BON cell line, demonstrates high affinity binding of the bombesin (BN) and somatostatin (SST) receptor-specific ligands. In the present study, BON cells, as a representative model, were further applied to evaluate various peptide analogs and cytotoxic receptor-targeted peptide conjugates. We observed quick ligand-receptor internalization in BON cells as well as high binding affinity. Furthermore, BON cells have high expression of multidrug resistance-associated genes (MDR1) and show camptothecin (CPT) resistance. Various receptor-specific cytotoxic conjugates were synthesized and evaluated in the BON cell model via in vitro and in vivo studies. We found that all the tested conjugates displayed potent antitumor ability in xenografts. Especially, the CPT conjugates, CPT-SST, and CPT-BN, are most likely to increase sensitivity to CPT-resistant BON cells. Our findings suggest that appropriately defined tumor cell lines may provide physiologically relevant cell-based evaluations of novel peptide analogs and receptor-targeted chemotherapeutics.
Insights
This study evaluated novel peptide conjugates targeting bombesin (BN) and somatostatin (SST) receptors in drug-resistant pancreatic cancer cells. Certain conjugates, particularly those with camptothecin (CPT), showed potent antitumor effects, enhancing sensitivity in resistant models.
Area of Science:
- Oncology
- Pharmacology
- Molecular Biology
Background:
- The human pancreatic carcinoid BON cell line exhibits high binding affinity for bombesin (BN) and somatostatin (SST) receptor ligands.
- BON cells display multidrug resistance (MDR1) and resistance to camptothecin (CPT).
Purpose of the Study:
- To evaluate peptide analogs and cytotoxic receptor-targeted peptide conjugates using the BON cell line as a model.
- To assess the efficacy of novel chemotherapeutic conjugates against CPT-resistant cancer cells.
Main Methods:
- Utilized the BON cell line for in vitro and in vivo studies of peptide conjugates.
- Synthesized and tested various receptor-specific cytotoxic conjugates, including CPT-SST and CPT-BN.
- Assessed ligand-receptor internalization, binding affinity, and antitumor activity in xenografts.
Main Results:
- BON cells demonstrated rapid ligand-receptor internalization and high binding affinity.
- All tested cytotoxic conjugates exhibited significant antitumor activity in vivo.
- CPT conjugates (CPT-SST, CPT-BN) notably increased sensitivity in CPT-resistant BON cells.
Conclusions:
- Appropriately selected tumor cell lines offer physiologically relevant models for evaluating novel peptide analogs.
- Receptor-targeted chemotherapeutics, especially CPT conjugates, show promise for overcoming drug resistance in pancreatic cancer.
