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DOI 10.34014/2227-1848-2025-1-114-123

BOMBESIN RECEPTOR ANTAGONIST BBN/C1-C2 IN AN IN VITRO MODEL FOR COLORECTAL CANCER

E.A. Beloborodov, E.V. Yurova, D.E. Sugak, A.N. Fomin, Yu.V. Saenko

Ulyanovsk State University, Ulyanovsk, Russia

 

Colorectal cancer is the third most common cancer and the second most fatal cancer worldwide. One of the strategies for colorectal cancer treatment is targeted peptide therapy that targets certain types of receptors overexpressed on the cell surface. A promising target is a bombesin receptor GRPR, which is abnormally expressed in colorectal cancer.

In this paper, we suggest to use BBN/C1-C2 molecule, created on the basis of bombesin, a peptide tropic to GRPR, and knottin, acting as a scaffold to stabilize a molecule, for colorectal cancer treatment. BBN/C1-C2 acts as a GRPR receptor antagonist, which determines BBN/C1-C2 role in the survival of cancer cells.

Objective: The aim of the paper is to study the effect of BBN/C1-C2 peptide on colorectal cancer cell survival.

Materials and Methods. The effect of BBN/C1-C2 peptide obtained by solid-phase synthesis on cancer cell survival was assessed in HCT-116 culture using fluorescence microscopy (apoptosis, necrosis) and a cell analyzer (cell adhesion dynamics) 3 and 24 hours after exposure.

Results: The BBN/C1-C2 peptide (concentrations from 0.2 to 20 μM) was able not only to inhibit cell proliferation, but also to cause cell death (apoptosis) three hours after incubation.

Conclusion. BBN/C12-C2 molecule, created on the basis of a GRPR agonist built into a knottin molecule, can be considered as a prototype for a radiopharmaceutical to treat colon tumors.

Key words: colorectal cancer, bombesin, targeted therapy.

 

Conflict of interest. The authors declare no conflict of interest.

Author contributions

Research concept and design: Saenko Yu.V., Fomin A.N.

Literature search, participation in the study, data processing: Beloborodov E.A., Yurova E.V., Sugak D.E.

Statistical data processing: Beloborodov E.A.

Data analysis and interpretation: Yurova E.V.

Text writing and editing: Beloborodov E.A., Yurova E.V., Saenko Yu.V.

 

References

  1. Hossain M.S., Karuniawati H., Jairoun A.A., Urbi Z., Ooi J., John A., Lim Y.C., Kibria K.M.K., Mohiuddin A.K.M., Ming L.C., Goh K.W., Hadi M.A. Colorectal Cancer: A Review of Carcinogenesis, Global Epidemiology, Current Challenges, Risk Factors, Preventive and Treatment Strategies. Cancers (Basel). 2022; 14 (7): 1732. DOI: 10.3390/cancers14071732.

  2. Safiejko K., Tarkowski R., Koselak M., Juchimiuk M., Tarasik A., Pruc M., Smereka J., Szarpak L. Robotic-Assisted vs. Standard Laparoscopic Surgery for Rectal Cancer Resection: A Systematic Review and Meta-Analysis of 19,731 Patients. Cancers (Basel). 2021; 14 (1): 180. DOI: 10.3390/cancers14010180.

  3. Dawson H., Kirsch R., Messenger D., Driman D. A Review of Current Challenges in Colorectal Cancer Reporting. Arch Pathol Lab Med. 2019; 143 (7): 869–882. DOI: 10.5858/arpa.2017-0475-RA.

  4. Dallas N.A., Xia L., Fan F., Gray M.J., Gaur P., van Buren G. 2nd, Samuel S., Kim M.P., Lim S.J., Ellis L.M. Chemoresistant colorectal cancer cells, the cancer stem cell phenotype, and increased sensitivity to insulin-like growth factor-I receptor inhibition. Cancer Res. 2009; 69 (5): 1951–1957. DOI: 10.1158/0008-5472.CAN-08-2023.

  5. Da Silva W.C., de Araujo V.E., Lima E.M.E.A., Dos Santos J.B.R., Silva M.R.R.D., Almeida P.H.R.F., de Assis Acurcio F., Godman B., Kurdi A., Cherchiglia M.L., Andrade E.I.G. Comparative Effectiveness and Safety of Monoclonal Antibodies (Bevacizumab, Cetuximab, and Panitumumab) in Combination with Chemotherapy for Metastatic Colorectal Cancer: A Systematic Review and Meta-Analysis. BioDrugs. 2018; 32 (6): 585–606. DOI: 10.1007/s40259-018-0322-1.

  6. Mooi J.K., Wirapati P., Asher R., Lee C.K., Savas P., Price T.J., Townsend A., Hardingham J., Buchanan D., Williams D., Tejpar S., Mariadason J.M., Tebbutt N.C. The prognostic impact of consensus molecular subtypes (CMS) and its predictive effects for bevacizumab benefit in metastatic colorectal cancer: molecular analysis of the AGITG MAX clinical trial. Ann Oncol. 2018; 29 (11): 2240–2246. DOI: 10.1093/annonc/mdy410.

  7. Tang P.A., Cohen S.J., Kollmannsberger C., Bjarnason G., Virik K., MacKenzie M.J., Lourenco L., Wang L., Chen A., Moore M.J. Phase II clinical and pharmacokinetic study of aflibercept in patients with previously treated metastatic colorectal cancer. Clin Cancer Res. 2012; 18 (21): 6023–6031. DOI: 10.1158/1078-0432.CCR-11-3252.

  8. Khan K., Valeri N., Dearman C., Rao S., Watkins D., Starling N., Chau I., Cunningham D. Targeting EGFR pathway in metastatic colorectal cancer- tumour heterogeniety and convergent evolution. Crit Rev Oncol Hematol. 2019; 143: 153–163. DOI: 10.1016/j.critrevonc.2019.09.001.

  9. Mendelsohn J., Baselga J. Epidermal growth factor receptor targeting in cancer. Semin Oncol. 2006;33 (4): 369–385. DOI: 10.1053/j.seminoncol.2006.04.003.

  10. Khan A.Z., Morris-Stiff G., Makuuchi M. Patterns of chemotherapy-induced hepatic injury and their implications for patients undergoing liver resection for colorectal liver metastases. J Hepatobiliary Pancreat Surg. 2009; 16 (2): 137–144. DOI: 10.1007/s00534-008-0016-z.

  11. Jensen R.T., Battey J.F., Spindel E.R., Benya R.V. International Union of Pharmacology. LXVIII. Mammalian bombesin receptors: nomenclature, distribution, pharmacology, signaling, and functions in normal and disease states. Pharmacol Rev. 2008; 60 (1): 1–42. DOI: 10.1124/pr.107.07108.

  12. Sun H.L., Ma Q.Y., Bian H.G, Meng X.M., Jin J. Novel insight on GRP/GRPR axis in diseases. Biomed Pharmacother. 2023; 161: 114497. DOI: 10.1016/j.biopha.2023.114497.

  13. Welton M. L., Mantyh C. R., Gates T. S., Popper P., Vigna S. R., Maggio J.E., Mantyh P.W. Localization of Bombesin Receptors in the Human Gastrointestinal Tract Using Quantitative Receptor Autoradiography. Pharmacology. 1988; 547 (1): 468–470. DOI: https://doi.org/10.1111/j.1749-6632.1988.tb23922.x.

  14. Carroll R.E., Matkowskyj K.A., Chakrabarti S., McDonald T.J., Benya R.V. Aberrant expression of gastrin-releasing peptide and its receptor by well-differentiated colon cancers in humans. Am J Physiol. 1999; 276 (3): G655-65. DOI: 10.1152/ajpgi.1999.276.3.G655.

  15. Khokhlova A., Zolotovskii I., Pogodina E., Saenko Y., Stoliarov D., Vorsina S., Fotiadi A., Liamina D., Sokolovski S., Rafailov E. Effects of high and low level 1265 nm laser irradiation on HCT116 cancer cells. Proceedings of the SPIE. 2019; 10861. DOI: https://doi.org/10.1117/12.2509529.

  16. Ke N., Wang X., Xu X., Abassi Y.A. The xCELLigence system for real-time and label-free monitoring of cell viability. Methods Mol Biol. 2011; 740: 33–43. DOI: 10.1007/978-1-61779-108-6_6.

  17. Ma Y., Gao F. Advances of radiolabeled GRPR ligands for PET/CT imaging of cancers. Cancer Imaging. 2024; 24 (1): 19. DOI: 10.1186/s40644-024-00658-y.

  18. Kanellopoulos P., Mattsson A., Abouzayed A., Obeid K., Nock B.A., Tolmachev V., Maina T., Orlova A. Preclinical evaluation of new GRPR-antagonists with improved metabolic stability for radiotheranostic use in oncology. EJNMMI Radiopharm Chem. 2024; 9 (1): 13. DOI: 10.1186/s41181-024-00242-6.

  19. Maddalena M.E., Fox J., Chen J., Feng W., Cagnolini A., Linder K.E., Tweedle M.F., Nunn A.D., Lantry L.E. 177Lu-AMBA biodistribution, radiotherapeutic efficacy, imaging, and autoradiography in prostate cancer models with low GRP-R expression. J Nucl Med. 2009; 50 (12): 2017–2024. DOI: 10.2967/jnumed.109.064444.

  20. Wild D., Frischknecht M., Zhang H., Morgenstern A., Bruchertseifer F., Boisclair J., Provencher-Bolliger A., Reubi J.C., Maecke H.R. Alpha- versus beta-particle radiopeptide therapy in a human prostate cancer model (213Bi-DOTA-PESIN and 213Bi-AMBA versus 177Lu-DOTA-PESIN). Cancer Res. 2011; 71 (3): 1009–1018. DOI: 10.1158/0008-5472.CAN-10-1186.

  21. Okarvi S.M., Jammaz I.A. Preparation and evaluation of bombesin peptide derivatives as potential tumor imaging agents: effects of structure and composition of amino acid sequence on in vitro and in vivo characteristics. Nucl Med Biol. 2012; 39 (6): 795–804. DOI: 10.1016/j.nucmedbio.2012.01.002.

  22. Bodei L., Ferrari M., Nunn A., Llull J., Cremonesi M., Martano L., Laurora G., Scardino E., Tiberini S., Bufi G., Eaton S., Ottavio de Cobelli, Paganelli G. Lu-177-AMBA Bombesin Analogue in Hormone Refractory Prostate Cancer Patients: A Phase i Escalation Study with Single-Cycle Administrations. Eur. J. Nucl. Med. Mol. 2007; 34: 221–221.

  23. Zhu Y., Wang H., Yu M., Li C., Meng X., He M., Yao R. Design, Synthesis and Biological Evaluation of Novel 1, 3, 4-Oxadiazole PD176252 Analogues as Potential GRPR Inhibitors. Anticancer Agents Med Chem. 2022; 22 (17): 3009–3024. DOI: 10.2174/1871520622666220501162813.

  24. Rick F.G., Buchholz S., Schally A.V., Szalontay L., Krishan A., Datz C., Stadlmayr A., Aigner E., Perez R., Seitz S., Block N.L., Hohla F. Combination of gastrin-releasing peptide antagonist with cytotoxic agents produces synergistic inhibition of growth of human experimental colon cancers. Cell Cycle. 2012; 11 (13): 2518–2525. DOI: 10.4161/cc.20900.

Received December 16, 2024; accepted February 02, 2025.

 

Information about the authors

Beloborodov Evgeniy Alekseevich, Researcher, S.P. Kapitsa Research Institute of Technology, Ulyanovsk State University. 432017, Russia, Ulyanovsk, L. Tolstoy St., 42; e-mail: This email address is being protected from spambots. You need JavaScript enabled to view it., ORCID ID: https://orcid.org/0000-0002-5666-5154

Yurova Elena Valer'evna, Junior Researcher, S.P. Kapitsa Research Institute of Technology, Ulyanovsk State University. 432017, Russia, Ulyanovsk, L. Tolstoy St., 42; e-mail: This email address is being protected from spambots. You need JavaScript enabled to view it., ORCID ID: http://orcid.org/0000-0001-7484-2671

Sugak Dmitriy Evgen'evich, Junior Researcher S.P. Kapitsa Research Institute of Technology, Ulyanovsk State University. 432017, Russia, Ulyanovsk, L. Tolstoy St., 42; e-mail: This email address is being protected from spambots. You need JavaScript enabled to view it., ORCID ID: https://orcid.org/0000-0002-3276-8976

Fomin Aleksandr Nikolaevich, Candidate of Sciences (Engineering), Senior Researcher, S.P. Kapitsa Research Institute of Technology, Vice-Rector for Research, Ulyanovsk State University. 432017, Russia, Ulyanovsk, L. Tolstoy St., 42; e-mail: This email address is being protected from spambots. You need JavaScript enabled to view it., ORCID ID: https://orcid.org/0000-0003-0826-1857

Saenko Yuriy Vladimirovich, Doctor of Sciences (Biology), Leading Researcher S.P. Kapitsa Research Institute of Technology, Ulyanovsk State University. 432017, Russia, Ulyanovsk, L. Tolstoy St., 42; e-mail: This email address is being protected from spambots. You need JavaScript enabled to view it., ORCID ID: http://orcid.org/0000-0002-4402-1482

 

For citation

Beloborodov E.A., Yurova E.V., Sugak D.E., Fomin A.N., Saenko Yu.V. Antagonist bombezinovykh retseptorov BBN/C1-C2 v modeli kolorektal'nogo raka in vitro [Bombesin receptor antagonist BBN/C1-C2 in an in vitro model for colorectal cancer]. Ul'yanovskiy mediko-biologicheskiy zhurnal. 2025; 1: 114–123. DOI: 10.34014/2227-1848-2025-1-114-123 (in Russian).

 

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УДК 615.849.12;615.277.3

DOI 10.34014/2227-1848-2025-1-114-123

АНТАГОНИСТ БОМБЕЗИНОВЫХ РЕЦЕПТОРОВ BBN/C1-C2 В МОДЕЛИ КОЛОРЕКТАЛЬНОГО РАКА IN VITRO

Е.А. Белобородов, Е.В. Юрова, Д.Е. Сугак, А.Н. Фомин, Ю.В. Саенко

ФГБОУ ВО «Ульяновский государственный университет», г. Ульяновск, Россия

 

Колоректальный рак является третьим по распространенности и вторым по количеству смертей онкологическим заболеванием в мире. Одна из стратегий лечения колоректального рака заключается в использовании таргетной пептидной терапии, нацеленной на определенные типы рецепторов, сверхэкспрессирующихся на поверхности клеток. Перспективной мишенью является бомбезиновый рецептор GRPR, для которого характерна аномальная экспрессия при колоректальном раке.

В данной работе для лечения колоректального рака предлагается использовать молекулу BBN/C1-C2, созданную на основе бомбезина – короткого пептида, тропного к GRPR, и кноттина, который выступает в качестве каркаса для стабилизации молекулы. BBN/C1-C2 выступает в роли антагониста рецептора GRPR, что определяет его роль в выживаемости раковых клеток.

Цель. Изучение влияния пептида BBN/C1-C2 на выживаемость клеточной культуры колоректального рака.

Материалы и методы. Влияние пептида BBN/C1-C2, полученного с помощью твердофазного синтеза, на выживаемость раковых клеток оценивали в культуре HCT-116 с использованием флуоресцентной микроскопии (апоптоз, некроз) и клеточного анализатора (динамика адгезии клеток) через 3 и 24 ч после воздействия.

Результаты. Пептид BBN/C1-C2 в концентрациях от 0,2 до 20 мкМ показал себя как молекулу, способную не только ингибировать пролиферацию клеток, но и вызывать клеточную гибель путем апоптоза уже через три часа после инкубации.

Выводы. Таким образом, молекула BBN/C12-C2, созданная на основе агониста GRPR, встроенного в молекулу кноттина, может рассматриваться в качестве прототипа для создания радиофармпрепарата для лечения новообразований толстого кишечника.

Ключевые слова: колоректальный рак, бомбезин, таргетная терапия.

 

Конфликт интересов. Авторы заявляют об отсутствии конфликта интересов.

Вклад авторов

Концепция и дизайн исследования: Саенко Ю.В., Фомин А.Н.

Литературный поиск, участие в исследовании, обработка материала: Белобородов Е.А., Юрова Е.В., Сугак Д.Е.

Статистическая обработка данных: Белобородов Е.А.

Анализ и интерпретация данных: Юрова Е.В.

Написание и редактирование текста: Белобородов Е.А., Юрова Е.В., Саенко Ю.В.

 

Литература

  1. Hossain M.S., Karuniawati H., Jairoun A.A., Urbi Z., Ooi J., John A., Lim Y.C., Kibria K.M.K., Mohiuddin A.K.M., Ming L.C., Goh K.W., Hadi M.A. Colorectal Cancer: A Review of Carcinogenesis, Global Epidemiology, Current Challenges, Risk Factors, Preventive and Treatment Strategies. Cancers (Basel). 2022; 14 (7): 1732. DOI: 10.3390/cancers14071732.

  2. Safiejko K., Tarkowski R., Koselak M., Juchimiuk M., Tarasik A., Pruc M., Smereka J., Szarpak L. Robotic-Assisted vs. Standard Laparoscopic Surgery for Rectal Cancer Resection: A Systematic Review and Meta-Analysis of 19,731 Patients. Cancers (Basel). 2021; 14 (1): 180. DOI: 10.3390/cancers14010180.

  3. Dawson H., Kirsch R., Messenger D., Driman D. A Review of Current Challenges in Colorectal Cancer Reporting. Arch Pathol Lab Med. 2019; 143 (7): 869–882. DOI: 10.5858/arpa.2017-0475-RA.

  4. Dallas N.A., Xia L., Fan F., Gray M.J., Gaur P., van Buren G. 2nd, Samuel S., Kim M.P., Lim S.J., Ellis L.M. Chemoresistant colorectal cancer cells, the cancer stem cell phenotype, and increased sensitivity to insulin-like growth factor-I receptor inhibition. Cancer Res. 2009; 69 (5): 1951–1957. DOI: 10.1158/0008-5472.CAN-08-2023.

  5. Da Silva W.C., de Araujo V.E., Lima E.M.E.A., Dos Santos J.B.R., Silva M.R.R.D., Almeida P.H.R.F., de Assis Acurcio F., Godman B., Kurdi A., Cherchiglia M.L., Andrade E.I.G. Comparative Effectiveness and Safety of Monoclonal Antibodies (Bevacizumab, Cetuximab, and Panitumumab) in Combination with Chemotherapy for Metastatic Colorectal Cancer: A Systematic Review and Meta-Analysis. BioDrugs. 2018; 32 (6): 585–606. DOI: 10.1007/s40259-018-0322-1.

  6. Mooi J.K., Wirapati P., Asher R., Lee C.K., Savas P., Price T.J., Townsend A., Hardingham J., Buchanan D., Williams D., Tejpar S., Mariadason J.M., Tebbutt N.C. The prognostic impact of consensus molecular subtypes (CMS) and its predictive effects for bevacizumab benefit in metastatic colorectal cancer: molecular analysis of the AGITG MAX clinical trial. Ann Oncol. 2018; 29 (11): 2240–2246. DOI: 10.1093/annonc/mdy410.

  7. Tang P.A., Cohen S.J., Kollmannsberger C., Bjarnason G., Virik K., MacKenzie M.J., Lourenco L., Wang L., Chen A., Moore M.J. Phase II clinical and pharmacokinetic study of aflibercept in patients with previously treated metastatic colorectal cancer. Clin Cancer Res. 2012; 18 (21): 6023–6031. DOI: 10.1158/1078-0432.CCR-11-3252.

  8. Khan K., Valeri N., Dearman C., Rao S., Watkins D., Starling N., Chau I., Cunningham D. Targeting EGFR pathway in metastatic colorectal cancer- tumour heterogeniety and convergent evolution. Crit Rev Oncol Hematol. 2019; 143: 153–163. DOI: 10.1016/j.critrevonc.2019.09.001.

  9. Mendelsohn J., Baselga J. Epidermal growth factor receptor targeting in cancer. Semin Oncol. 2006; 33 (4): 369–385. DOI: 10.1053/j.seminoncol.2006.04.003.

  10. Khan A.Z., Morris-Stiff G., Makuuchi M. Patterns of chemotherapy-induced hepatic injury and their implications for patients undergoing liver resection for colorectal liver metastases. J Hepatobiliary Pancreat Surg. 2009; 16 (2): 137–144. DOI: 10.1007/s00534-008-0016-z.

  11. Jensen R.T., Battey J.F., Spindel E.R., Benya R.V. International Union of Pharmacology. LXVIII. Mammalian bombesin receptors: nomenclature, distribution, pharmacology, signaling, and functions in normal and disease states. Pharmacol Rev. 2008; 60 (1): 1–42. DOI: 10.1124/pr.107.07108.

  12. Sun H.L., Ma Q.Y., Bian H.G, Meng X.M., Jin J. Novel insight on GRP/GRPR axis in diseases. Biomed Pharmacother. 2023; 161: 114497. DOI: 10.1016/j.biopha.2023.114497.

  13. Welton M. L., Mantyh C. R., Gates T. S., Popper P., Vigna S. R., Maggio J.E., Mantyh P.W. Localization of Bombesin Receptors in the Human Gastrointestinal Tract Using Quantitative Receptor Autoradiography. Pharmacology. 1988; 547 (1): 468–470. DOI: https://doi.org/10.1111/j.1749-6632.1988.tb23922.x.

  14. Carroll R.E., Matkowskyj K.A., Chakrabarti S., McDonald T.J., Benya R.V. Aberrant expression of gastrin-releasing peptide and its receptor by well-differentiated colon cancers in humans. Am J Physiol. 1999; 276 (3): G655-65. DOI: 10.1152/ajpgi.1999.276.3.G655.

  15. Khokhlova A., Zolotovskii I., Pogodina E., Saenko Y., Stoliarov D., Vorsina S., Fotiadi A., Liamina D., Sokolovski S., Rafailov E. Effects of high and low level 1265 nm laser irradiation on HCT116 cancer cells. Proceedings of the SPIE. 2019; 10861. DOI: https://doi.org/10.1117/12.2509529.

  16. Ke N., Wang X., Xu X., Abassi Y.A. The xCELLigence system for real-time and label-free monitoring of cell viability. Methods Mol Biol. 2011; 740: 33–43. DOI: 10.1007/978-1-61779-108-6_6.

  17. Ma Y., Gao F. Advances of radiolabeled GRPR ligands for PET/CT imaging of cancers. Cancer Imaging. 2024; 24 (1): 19. DOI: 10.1186/s40644-024-00658-y.

  18. Kanellopoulos P., Mattsson A., Abouzayed A., Obeid K., Nock B.A., Tolmachev V., Maina T., Orlova A. Preclinical evaluation of new GRPR-antagonists with improved metabolic stability for radiotheranostic use in oncology. EJNMMI Radiopharm Chem. 2024; 9 (1): 13. DOI: 10.1186/s41181-024-00242-6.

  19. Maddalena M.E., Fox J., Chen J., Feng W., Cagnolini A., Linder K.E., Tweedle M.F., Nunn A.D., Lantry L.E. 177Lu-AMBA biodistribution, radiotherapeutic efficacy, imaging, and autoradiography in prostate cancer models with low GRP-R expression. J Nucl Med. 2009; 50 (12): 2017–2024. DOI: 10.2967/jnumed.109.064444.

  20. Wild D., Frischknecht M., Zhang H., Morgenstern A., Bruchertseifer F., Boisclair J., Provencher-Bolliger A., Reubi J.C., Maecke H.R. Alpha- versus beta-particle radiopeptide therapy in a human prostate cancer model (213Bi-DOTA-PESIN and 213Bi-AMBA versus 177Lu-DOTA-PESIN). Cancer Res. 2011; 71 (3): 1009–1018. DOI: 10.1158/0008-5472.CAN-10-1186.

  21. Okarvi S.M., Jammaz I.A. Preparation and evaluation of bombesin peptide derivatives as potential tumor imaging agents: effects of structure and composition of amino acid sequence on in vitro and in vivo characteristics. Nucl Med Biol. 2012; 39 (6): 795–804. DOI: 10.1016/j.nucmedbio.2012.01.002.

  22. Bodei L., Ferrari M., Nunn A., Llull J., Cremonesi M., Martano L., Laurora G., Scardino E., Tiberini S., Bufi G., Eaton S., Ottavio de Cobelli, Paganelli G. Lu-177-AMBA Bombesin Analogue in Hormone Refractory Prostate Cancer Patients: A Phase i Escalation Study with Single-Cycle Administrations. Eur. J. Nucl. Med. Mol. 2007; 34: 221–221.

  23. Zhu Y., Wang H., Yu M., Li C., Meng X., He M., Yao R. Design, Synthesis and Biological Evaluation of Novel 1, 3, 4-Oxadiazole PD176252 Analogues as Potential GRPR Inhibitors. Anticancer Agents Med Chem. 2022; 22 (17): 3009–3024. DOI: 10.2174/1871520622666220501162813.

  24. Rick F.G., Buchholz S., Schally A.V., Szalontay L., Krishan A., Datz C., Stadlmayr A., Aigner E., Perez R., Seitz S., Block N.L., Hohla F. Combination of gastrin-releasing peptide antagonist with cytotoxic agents produces synergistic inhibition of growth of human experimental colon cancers. Cell Cycle. 2012; 11 (13): 2518–2525. DOI: 10.4161/cc.20900.

Поступила в редакцию 16.12.2024; принята 02.02.2025.

 

Авторский коллектив

Белобородов Евгений Алексеевич – научный сотрудник НИТИ имени С.П. Капицы, ФГБОУ ВО «Ульяновский государственный университет». 432017, Россия, г. Ульяновск, ул. Л. Толстого, 42; e-mail: This email address is being protected from spambots. You need JavaScript enabled to view it., ORCID ID: https://orcid.org/0000-0002-5666-5154

Юрова Елена Валерьевна – младший научный сотрудник НИТИ имени С.П. Капицы, ФГБОУ ВО «Ульяновский государственный университет». 432017, Россия, г. Ульяновск, ул. Л. Толстого, 42; e-mail: This email address is being protected from spambots. You need JavaScript enabled to view it., ORCID ID: http://orcid.org/0000-0001-7484-2671

Сугак Дмитрий Евгеньевич – младший научный сотрудник НИТИ имени С.П. Капицы, ФГБОУ ВО «Ульяновский государственный университет». 432017, Россия, г. Ульяновск, ул. Л. Толстого, 42; e-mail: This email address is being protected from spambots. You need JavaScript enabled to view it., ORCID ID: https://orcid.org/0000-0002-3276-8976

Фомин Александр Николаевич – кандидат технических наук, старший научный сотрудник НИТИ имени С.П. Капицы, проректор на научной работе, ФГБОУ ВО «Ульяновский государственный университет». 432017, Россия, г. Ульяновск, ул. Л. Толстого, 42; e-mail: This email address is being protected from spambots. You need JavaScript enabled to view it., ORCID ID: https://orcid.org/0000-0003-0826-1857

Саенко Юрий Владимирович – доктор биологических наук, ведущий научный сотрудник НИТИ имени С.П. Капицы, ФГБОУ ВО «Ульяновский государственный университет». 432017, Россия, г. Ульяновск, ул. Л. Толстого, 42; e-mail: This email address is being protected from spambots. You need JavaScript enabled to view it., ORCID ID: http://orcid.org/0000-0002-4402-1482

 

Образец цитирования

Белобородов Е.А., Юрова Е.В., Сугак Д.Е., Фомин А.Н., Саенко Ю.В. Антагонист бомбезиновых рецепторов BBN/C1-C2 в модели колоректального рака in vitro. Ульяновский медико-биологический журнал. 2025; 1: 114–123. DOI: 10.34014/2227-1848-2025-1-114-123.