-
Preclinical Efficacy of [V4 Q5 ]dDAVP, a Second Generation Vasopressin Analog, on Metastatic Spread and Tumor-Associated Angiogenesis in Colorectal Cancer
-
Juan Garona, Natasha T. Sobol, Marina Pifano, Valeria I. Segatori, Daniel E. Gomez, Giselle V. Ripoll, Daniel F. Alonso
-
Cancer Res Treat. 2019;51(2):438-450. Published online June 1, 2018
-
DOI: https://doi.org/10.4143/crt.2018.040
-
-
Abstract
PDFSupplementary MaterialPubReaderePub
- Purpose
Control of metastatic spread of colorectal cancer (CRC) remains as a major therapeutic challenge. [V4 Q5 ]dDAVP is a vasopressin peptide analog with previously reported anticancer activity against carcinoma tumors. By acting as a selective agonist of arginine vasopressin type 2 membrane receptor (AVPR2) present in endothelial and tumor cells, [V4Q5]dDAVP is able to impair tumor aggressiveness and distant spread. Our aim was to evaluate the potential therapeutic benefits of [V4Q5]dDAVP on highly aggressive CRC disease using experimental models with translational relevance.
Materials and Methods
Murine CT-26 and human Colo-205 AVPR2-expressing CRC cell lines were used to test the preclinical efficacy of [V4Q5]dDAVP, both in vitro and in vivo.
Results
In syngeneic mice surgically implanted with CT-26 cells in the spleen, sustained intravenous treatment with [V4Q5]dDAVP (0.3 µg/kg) dramatically impaired metastatic progression to liver without overt signs of toxicity, and also reduced experimental lung colonization. The compound inhibited in vivo angiogenesis driven by Colo-205 cells in athymic mice, as well as in vitro endothelial cell migration and capillary tube formation. [V4Q5]dDAVP exerted AVPR2-dependent cytostatic activity in vitro (IC50 1.08 µM) and addition to 5-fluorouracil resulted in synergistic antiproliferative effects both in CT-26 and Colo-205 cells.
Conclusion
The present preclinical study establishes for the first time the efficacy of [V4Q5]dDAVP on CRC. These encouraging results suggest that the novel second generation vasopressin analog could be used for the management of aggressive CRC as an adjuvant agent during surgery or to complement standard chemotherapy, limiting tumor angiogenesis and metastasis and thus protecting the patient from CRC recurrence.
-
Citations
Citations to this article as recorded by
- Gastrointestinal digestion of food proteins: Anticancer, antihypertensive, anti-obesity, and immunomodulatory mechanisms of the derived peptides
Zheng Yan, Yang Gui, Chunhong Liu, Xiaohai Zhang, Chaoling Wen, Opeyemi Joshua Olatunji, Itthanan Suttikhana, Tolulope Joshua Ashaolu Food Research International.2024; 189: 114573. CrossRef - AVPR2 is a potential prognostic biomarker and correlated with immune infiltration in head and neck squamous cell carcinoma
Linwei Mao, Zhiyong Pan, Wenzhi Chen, Weiqun Hu, Xiufen Chen, Huiting Dai BMC Medical Genomics.2023;[Epub] CrossRef - Circulating Levels of the Cardiovascular Biomarkers ST2 and Adrenomedullin Predict Outcome within a Randomized Phase III Lung Cancer Trial (RASTEN)
Emelie Gezelius, Pär-Ola Bendahl, Widet Gallo, Kelin Gonçalves de Oliveira, Lars Ek, Bengt Bergman, Jan Sundberg, Olle Melander, Mattias Belting Cancers.2022; 14(5): 1307. CrossRef - Vasopressin and Its Analogues: From Natural Hormones to Multitasking Peptides
Mladena Glavaš, Agata Gitlin-Domagalska, Dawid Dębowski, Natalia Ptaszyńska, Anna Łęgowska, Krzysztof Rolka International Journal of Molecular Sciences.2022; 23(6): 3068. CrossRef - Identification of Hub Genes of Lung Adenocarcinoma Based on Weighted Gene Co-Expression Network in Chinese Population
Yuning Xie, Hongjiao Wu, Wenqian Hu, Hongmei Zhang, Ang Li, Zhi Zhang, Shuhua Ren, Xuemei Zhang Pathology and Oncology Research.2022;[Epub] CrossRef - Propranolol blocks osteosarcoma cell cycle progression, inhibits angiogenesis and slows xenograft growth in combination with cisplatin-based chemotherapy
Luisina M. Solernó, Natasha T. Sobol, María F. Gottardo, Carla S. Capobianco, Maximiliano R. Ferrero, Liliana Vásquez, Daniel F. Alonso, Juan Garona Scientific Reports.2022;[Epub] CrossRef - Genetic Determination of Regressive Pattern of Walker 256 Carcinosarcoma in Rats with Hypothalamic Diabetes Insipidus
I. I. Khegay Bulletin of Experimental Biology and Medicine.2022; 173(4): 441. CrossRef - Vasopressin Receptors in Blood Vessels and Proliferation of Endotheliocytes
I. I. Khegay Russian Journal of Bioorganic Chemistry.2021; 47(4): 815. CrossRef - Targeting the vasopressin type-2 receptor for renal cell carcinoma therapy
Sonali Sinha, Nidhi Dwivedi, Shixin Tao, Abeda Jamadar, Vijayakumar R. Kakade, Maura O’ Neil, Robert H. Weiss, Jonathan Enders, James P. Calvet, Sufi M. Thomas, Reena Rao Oncogene.2020; 39(6): 1231. CrossRef - Administration of the vasopressin analog desmopressin for the management of bleeding in rectal cancer patients: results of a phase I/II trial
Soledad Iseas, Enrique L. Roca, Juan M. O’Connor, Martin Eleta, Analia Sanchez-Luceros, Daniela Di Leo, Marcelo Tinelli, Maria L. Fara, Eduardo Spitzer, Ignacio A. Demarco, Giselle V. Ripoll, Marina Pifano, Juan Garona, Daniel F. Alonso Investigational New Drugs.2020; 38(5): 1580. CrossRef - The Anticancer Properties of Tanshinones and the Pharmacological Effects of Their Active Ingredients
Li Fu, Bing Han, Yang Zhou, Jie Ren, Wenzhi Cao, Gopal Patel, Guoyin Kai, Jun Zhang Frontiers in Pharmacology.2020;[Epub] CrossRef - Potential Use of Desmopressin During Hepatic Resection for Colorectal Liver Metastases*
Juan Garona, Natasha T. Sobol, Luisina M. Solernó, Daniel F. Alonso Journal of Surgical Research.2019; 237: 1. CrossRef
-
9,721
View
-
280
Download
-
18
Web of Science
-
12
Crossref
|