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BREAST CANCER / EXPERIMENTAL RESEARCH
P2X7 blockade inhibits the growth of breast cancer in 4T1 breast cancer-bearing mice by NLRP3/caspase 1 pathway
1
Department of Obstetrics and Gynecology, Affiliated TCM Hospital of Southwest Medical University, Sichuan, China
2
Medicine Experimental Center, The Affiliated Hospital of Southwest Medical University, Sichuan, China
3
Cancer Research Institute of SouthWest Medical University, Sichuan, China
4
Department of Pathology, Affiliated Hospital of Southwest Medical University, Sichuan, China
Submission date: 2020-03-26
Final revision date: 2020-06-10
Acceptance date: 2020-06-21
Online publication date: 2020-09-15
Publication date: 2026-06-30
Corresponding author
Yong Liu
Department of Pathology The Affiliated Hospital Southwest Medical University Luzhou, Sichuan, China
Department of Pathology The Affiliated Hospital Southwest Medical University Luzhou, Sichuan, China
Arch Med Sci 2026;22(3):1856-1863
KEYWORDS
TOPICS
ABSTRACT
Introduction:
The role of P2X7 in the progression of breast cancer remains unclear; hence, it is necessary to investigate whether the P2X7/NLRP3/caspase 1 signalling pathway is associated with the development of breast cancer.
Material and methods:
4T1 breast cancer-bearing mice models were developed for P2X7 agonists BzATP and antagonists BBG. The weight of breast cancer tissue among groups was calculated and compared. The cancer tissue was observed by haematoxylin and eosin (HE) staining, and the expression of P2X7, NLRP3, and caspase 1 was examined by immunofluorescence and western blot.
Results:
The tumour weight and the medullary lymphocytes in the BzATP group were significantly higher than those of the sham and control groups, but the tumour weight and the medullary lymphocytes in the BBG group were significantly lower than those of the sham, control, and BzATP groups. The number of positive P2X7 in the BzATP group was significantly higher than that of other groups, but BBG significantly reduced the number of P2X7. The relative expression level of P2X7 in the BzATP group was significantly higher than that of other groups, but the relative expression level of P2X7 in the BBG group was significantly lower than that of other breast cancer-bearing groups.
Conclusions:
The blocking of P2X7 can inhibit the growth of breast cancer in 4T1 breast cancer-bearing mice via NLRP3/caspase 1 pathway. Future studies are needed to elucidate the underlying mechanism.
The role of P2X7 in the progression of breast cancer remains unclear; hence, it is necessary to investigate whether the P2X7/NLRP3/caspase 1 signalling pathway is associated with the development of breast cancer.
Material and methods:
4T1 breast cancer-bearing mice models were developed for P2X7 agonists BzATP and antagonists BBG. The weight of breast cancer tissue among groups was calculated and compared. The cancer tissue was observed by haematoxylin and eosin (HE) staining, and the expression of P2X7, NLRP3, and caspase 1 was examined by immunofluorescence and western blot.
Results:
The tumour weight and the medullary lymphocytes in the BzATP group were significantly higher than those of the sham and control groups, but the tumour weight and the medullary lymphocytes in the BBG group were significantly lower than those of the sham, control, and BzATP groups. The number of positive P2X7 in the BzATP group was significantly higher than that of other groups, but BBG significantly reduced the number of P2X7. The relative expression level of P2X7 in the BzATP group was significantly higher than that of other groups, but the relative expression level of P2X7 in the BBG group was significantly lower than that of other breast cancer-bearing groups.
Conclusions:
The blocking of P2X7 can inhibit the growth of breast cancer in 4T1 breast cancer-bearing mice via NLRP3/caspase 1 pathway. Future studies are needed to elucidate the underlying mechanism.
REFERENCES (41)
1.
Liang D, Li D, Liu J, et al. Trends and patterns of cancer mortality in North China (Hebei Province), 1973-2013. Sci Rep 2018; 8: 311.
2.
Fan L, Strasser-Weippl K, Li JJ, et al. Breast cancer in China. Lancet Oncol 2014; 15: e279-89.
3.
Momenimovahed Z, Salehiniya H. Epidemiological characteristics of and risk factors for breast cancer in the world. Breast Cancer 2019; 11: 151-64.
4.
Coughlin SS. Epidemiology of breast cancer in women. Adv Exp Med Biol 2019; 1152: 9-29.
5.
Garcia-Aranda M, Redondo M. Immunotherapy: a challenge of breast cancer treatment. Cancers 2019; 11: 1822.
6.
Basu A, Ramamoorthi G, Jia Y, et al. Immunotherapy in breast cancer: current status and future directions. Adv Cancer Res 2019; 143: 295-349.
7.
Edechi CA, Ikeogu N, Uzonna JE, et al. Regulation of immunity in breast cancer. Cancers 2019; 11: 1080.
8.
Keren L, Bosse M, Marquez D, et al. A structured tumor-immune microenvironment in triple negative breast cancer revealed by multiplexed ion beam imaging. Cell 2018; 174: 1373-87e19.
9.
Clift R, Souratha J, Garrovillo SA, et al. Remodeling the tumor microenvironment sensitizes breast tumors to anti-programmed death-ligand 1 immunotherapy. Cancer Res 2019; 79: 4149-59.
10.
Martinez-Outschoorn U, Sotgia F, Lisanti MP. Tumor microenvironment and metabolic synergy in breast cancers: critical importance of mitochondrial fuels and function. Semin Oncol 2014; 41: 195-216.
11.
Canale FP, Ramello MC, Nunez N, et al. CD39 expression defines cell exhaustion in tumor-infiltrating CD8(+) T cells. Cancer Res 2018; 78: 115-28.
12.
Gilbert SM, Oliphant CJ, Hassan S, et al. ATP in the tumour microenvironment drives expression of nfP2X7, a key mediator of cancer cell survival. Oncogene 2019; 38: 194-208.
13.
Park M, Kim J, Phuong NTT, et al. Involvement of the P2X7 receptor in the migration and metastasis of tamoxifen-resistant breast cancer: effects on small extracellular vesicles production. Sci Rep 2019; 9: 11587.
14.
Hope JM, Greenlee JD, King MR. Mechanosensitive ion channels: TRPV4 and P2X7 in disseminating cancer cells. Cancer J 2018; 24: 84-92.
15.
Adinolfi E, Giuliani AL, De Marchi E, et al. The P2X7 receptor: a main player in inflammation. Biochem Pharmacol 2018; 151: 234-44.
16.
Draganov D, Gopalakrishna-Pillai S, Chen YR, et al. Modulation of P2X4/P2X7/Pannexin-1 sensitivity to extracellular ATP via Ivermectin induces a non-apoptotic and inflammatory form of cancer cell death. Sci Rep 2015; 5: 16222.
17.
Tan C, Han LI, Zou L, et al. Expression of P2X7R in breast cancer tissue and the induction of apoptosis by the gene-specific shRNA in MCF-7 cells. Exp Ther Med 2015; 10: 1472-8.
18.
Huang S, Chen Y, Wu W, et al. miR-150 promotes human breast cancer growth and malignant behavior by targeting the pro-apoptotic purinergic P2X7 receptor. PLoS One 2013; 8: e80707.
19.
Thawkar BS, Kaur G. Inhibitors of NF-kappaB and P2X7/NLRP3/Caspase 1 pathway in microglia: novel therapeutic opportunities in neuroinflammation induced early-stage Alzheimer’s disease. J Neuroimmunol 2019; 326: 62-74.
20.
Bae JY, Lee SW, Shin YH, et al. P2X7 receptor and NLRP3 inflammasome activation in head and neck cancer. Oncotarget 2017; 8: 48972-82.
21.
Franceschini A, Capece M, Chiozzi P, et al. The P2X7 receptor directly interacts with the NLRP3 inflammasome scaffold protein. FASEB J 2015; 29: 2450-61.
22.
Ghiringhelli F, Apetoh L, Tesniere A, et al. Activation of the NLRP3 inflammasome in dendritic cells induces IL-1beta-dependent adaptive immunity against tumors. Nat Med 2009; 15: 1170-8.
23.
Smeda M, Kieronska A, Proniewski B, et al. Dual antiplatelet therapy with clopidogrel and aspirin increases mortality in 4T1 metastatic breast cancer-bearing mice by inducing vascular mimicry in primary tumour. Oncotarget 2018; 9: 17810-24.
24.
Wen Z, Mei B, Li H, et al. P2X7 participates in intracerebral hemorrhage-induced secondary brain injury in rats via MAPKs signaling pathways. Neurochem Res 2017; 42: 2372-83.
25.
Qi Y, Hu X, Cui J, et al. Combined use of insoluble beta-glucan from the cell wall of Candida albicans and cyclophosphamide: Validation in S180 tumor-bearing mice. Biomed Pharmacother 2018; 97: 1366-72.
26.
Im K, Mareninov S, Diaz MFP, et al. An introduction to performing immunofluorescence staining. Methods Mol Biol 2019; 1897: 299-311.
27.
Burnstock G. Purinergic signalling: therapeutic developments. Front Pharmacol 2017; 8: 661.
28.
Burnstock G, Knight GE. The potential of P2X7 receptors as a therapeutic target, including inflammation and tumour progression. Purinergic Signal 2018; 14: 1-18.
29.
De Marchi E, Orioli E, Dal Ben D, et al. P2X7 receptor as a therapeutic target. Adv Protein Chem Struct Biol 2016; 104: 39-79.
30.
Scarpellino G, Genova T, Munaron L. Purinergic P2X7 receptor: a cation channel sensitive to tumor microenvironment. Recent Pat Anticancer Drug Discov 2019; 14: 32-8.
31.
Adinolfi E, De Marchi E, Orioli E, et al. Role of the P2X7 receptor in tumor-associated inflammation. Curr Opin Pharmacol 2019; 47: 59-64.
32.
Arnaud-Sampaio VF, Rabelo ILA, Ulrich H, et al. The P2X7 receptor in the maintenance of cancer stem cells, chemoresistance and metastasis. Stem Cell Rev Rep 2020; 16: 288-300.
33.
Di Virgilio F, Giuliani AL, Vultaggio-Poma V, et al. Non-nucleotide agonists triggering P2X7 receptor activation and pore formation. Front Pharmacol 2018; 9: 39.
34.
Slater M, Danieletto S, Pooley M, et al. Differentiation between cancerous and normal hyperplastic lobules in breast lesions. Breast Cancer Res Treat 2004; 83: 1-10.
35.
Salvestrini V, Orecchioni S, Talarico G, et al. Extracellular ATP induces apoptosis through P2X7R activation in acute myeloid leukemia cells but not in normal hematopoietic stem cells. Oncotarget 2017; 8: 5895-908.
36.
Jelassi B, Anchelin M, Chamouton J, et al. Anthraquinone emodin inhibits human cancer cell invasiveness by antagonizing P2X7 receptors. Carcinogenesis 2013; 34: 1487-96.
37.
McKelvey KJ, Hudson AL, Back M, et al. Radiation, inflammation and the immune response in cancer. Mamm Genome 2018; 29: 843-65.
38.
Karki R, Man SM, Kanneganti TD. Inflammasomes and Cancer. Cancer Immunol Res 2017; 5: 94-9.
39.
Yao M, Fan X, Yuan B, et al. Berberine inhibits NLRP3 Inflammasome pathway in human triple-negative breast cancer MDA-MB-231 cell. BMC Complement Altern Med 2019; 19: 216.
40.
Raut PK, Kim SH, Choi DY, et al. Growth of breast cancer cells by leptin is mediated via activation of the inflammasome: critical roles of estrogen receptor signaling and reactive oxygen species production. Biochem Pharmacol 2019; 161: 73-88.
41.
Biber K, Bhattacharya A, Campbell BM, et al. Microglial drug targets in AD: opportunities and challenges in drug discovery and development. Front Pharmacol 2019; 10: 840.
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| eISSN: | 1896-9151 |
| ISSN: | 1734-1922 |
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