Sunitinib potentiates the cytotoxic effect of electrochemotherapy in pancreatic carcinoma cells.
ECT
bleomycin
electrochemotherapy
pancreas
pancreatic cancer
sunitinib
tyrosine-kinase inhibitors
Journal
Radiology and oncology
ISSN: 1581-3207
Titre abrégé: Radiol Oncol
Pays: Poland
ID NLM: 9317213
Informations de publication
Date de publication:
28 03 2022
28 03 2022
Historique:
received:
10
02
2022
accepted:
02
03
2022
pubmed:
29
3
2022
medline:
20
5
2022
entrez:
28
3
2022
Statut:
epublish
Résumé
One of the new treatment options for unresectable locally advanced pancreatic cancer is electrochemotherapy (ECT), a local ablative therapy that potentiates the entry of chemotherapeutic drugs into the cells, by the application of an electric field to the tumor. Its feasibility and safety were demonstrated in preclinical and clinical studies; however, there is a lack of preclinical studies assessing the actions of different drugs used in ECT, their mechanisms and interactions with other target drugs that are used in clinical practice. The aim of the study was to determine the cytotoxicity of two chemotherapeutic drugs usually used in ECT (bleomycin and cisplatin) in the BxPC-3 human pancreatic carcinoma cell line and evaluate the interactions of ECT with the targeted drug sunitinib. First, the cytotoxicity of ECT using both chemotherapeutics was determined. In the next part, the interactions of ECT and sunitinib were evaluated through determination of combined cytotoxicity, sunitinib targets and kinetics of cell death. The results demonstrate that ECT is effective in pancreatic cancer cell line, especially when bleomycin is used, with the onset of cell death in the first hours after the treatment, reaching a plateau at 20 hours after the treatment. Furthermore, we provide the rationale for combining ECT with bleomycin and the targeted drug sunitinib to potentiate cytotoxicity. The combined treatment of sunitinib and ECT was synergistic for bleomycin only at the highest used concentration of bleomycin 0.14 μM, whereas with lower doses of bleomycin, this effect was not observed. The interaction of ECT and treatment with sunitinib was confirmed by course of the cell death, also indicating on synergism. ECT and sunitinib combined treatment has clinical potential, and further studies are warranted.
Sections du résumé
BACKGROUND
One of the new treatment options for unresectable locally advanced pancreatic cancer is electrochemotherapy (ECT), a local ablative therapy that potentiates the entry of chemotherapeutic drugs into the cells, by the application of an electric field to the tumor. Its feasibility and safety were demonstrated in preclinical and clinical studies; however, there is a lack of preclinical studies assessing the actions of different drugs used in ECT, their mechanisms and interactions with other target drugs that are used in clinical practice.
MATERIALS AND METHODS
The aim of the study was to determine the cytotoxicity of two chemotherapeutic drugs usually used in ECT (bleomycin and cisplatin) in the BxPC-3 human pancreatic carcinoma cell line and evaluate the interactions of ECT with the targeted drug sunitinib. First, the cytotoxicity of ECT using both chemotherapeutics was determined. In the next part, the interactions of ECT and sunitinib were evaluated through determination of combined cytotoxicity, sunitinib targets and kinetics of cell death.
RESULTS
The results demonstrate that ECT is effective in pancreatic cancer cell line, especially when bleomycin is used, with the onset of cell death in the first hours after the treatment, reaching a plateau at 20 hours after the treatment. Furthermore, we provide the rationale for combining ECT with bleomycin and the targeted drug sunitinib to potentiate cytotoxicity. The combined treatment of sunitinib and ECT was synergistic for bleomycin only at the highest used concentration of bleomycin 0.14 μM, whereas with lower doses of bleomycin, this effect was not observed. The interaction of ECT and treatment with sunitinib was confirmed by course of the cell death, also indicating on synergism.
CONCLUSIONS
ECT and sunitinib combined treatment has clinical potential, and further studies are warranted.
Identifiants
pubmed: 35344644
pii: raon-2022-0009
doi: 10.2478/raon-2022-0009
pmc: PMC9122288
doi:
Substances chimiques
Antineoplastic Agents
0
Bleomycin
11056-06-7
Sunitinib
V99T50803M
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
164-172Informations de copyright
© 2022 Masa Bosnjak, Tanja Jesenko, Bostjan Markelc, Anja Cerovsek, Gregor Sersa, Maja Cemazar, published by Sciendo.
Références
Eur J Surg Oncol. 2021 Aug;47(8):1836-1846
pubmed: 33726951
Int J Surg. 2015 Jun;18:230-6
pubmed: 25917204
Eur J Surg Oncol. 2018 May;44(5):651-657
pubmed: 29402556
Anticancer Drugs. 2000 Mar;11(3):201-8
pubmed: 10831279
Bioelectrochemistry. 2018 Aug;122:84-92
pubmed: 29574322
Updates Surg. 2020 Dec;72(4):1089-1096
pubmed: 32399592
Pancreas. 2020 Oct;49(9):1168-1173
pubmed: 32898000
World J Gastroenterol. 2017 Jul 14;23(26):4767-4778
pubmed: 28765698
Radiol Oncol. 2015 Mar 25;49(2):147-54
pubmed: 26029026
Ann Surg Oncol. 2010 Jan;17(1):194-205
pubmed: 19856029
J Neuroinflammation. 2018 Jul 6;15(1):199
pubmed: 29980212
J Surg Oncol. 2014 Sep;110(3):320-7
pubmed: 24782355
Anticancer Drugs. 2010 Jan;21 Suppl 1:S3-11
pubmed: 20110785
Eur J Surg Oncol. 2020 Sep;46(9):1628-1633
pubmed: 32387070
Int J Radiat Oncol Biol Phys. 2017 Feb 1;97(2):313-322
pubmed: 28068239
Ann Surg Oncol. 2013 Dec;20 Suppl 3:S443-9
pubmed: 23128941
N Engl J Med. 2011 Feb 10;364(6):501-13
pubmed: 21306237
Cancer. 2005 Jul 15;104(2):427-38
pubmed: 15952180
Mol Cancer Ther. 2010 Jul;9(7):2068-78
pubmed: 20606044
Bioelectrochemistry. 2018 Feb;119:161-171
pubmed: 29024870
Acta Oncol. 2018 Jul;57(7):874-882
pubmed: 29577784
Biomed Res Int. 2018 Mar 19;2018:7364539
pubmed: 29750170
Radiol Oncol. 2020 Jun 20;54(3):347-352
pubmed: 32562533
Bioelectricity. 2019 Dec 1;1(4):204-213
pubmed: 34471824
Eur Radiol Exp. 2019 Jan 22;3(1):2
pubmed: 30671676
Bioelectrochemistry. 2021 Aug;140:107832
pubmed: 33984694
Adv Enzyme Regul. 1984;22:27-55
pubmed: 6382953
World J Gastrointest Oncol. 2021 Dec 15;13(12):2064-2075
pubmed: 35070042
Methods. 2001 Dec;25(4):402-8
pubmed: 11846609
Cancers (Basel). 2020 Dec 15;12(12):
pubmed: 33333941
Cancers (Basel). 2019 Aug 14;11(8):
pubmed: 31416294
Lancet Gastroenterol Hepatol. 2019 Dec;4(12):934-947
pubmed: 31648972
Cancers (Basel). 2021 Sep 03;13(17):
pubmed: 34503247
Semin Oncol. 2019 Apr;46(2):173-191
pubmed: 31122761