Beneficial effects of alpha-1 antitrypsin therapy in a mouse model of colitis-associated colon cancer
(2023) In BMC Cancer 23(1).- Abstract
Background: It is widely accepted that chronic inflammatory bowel diseases significantly higher a risk for colorectal cancer development. Among different types of treatments for patients with colon cancer, novel protein-based therapeutic strategies are considered. AIM: To explore the effect of human plasma alpha-1 antitrypsin (AAT) protein in the chemically induced mouse model of colorectal cancer. Methods: BALB/c mice with azoxymethane/dextran sodium sulfate (AOM/DSS)-induced colitis-associated colorectal cancer (CAC), we intraperitoneally treated with commercial preparation of human plasma AAT (4 mg per mouse). Effects of this therapy were evaluated histologically, and by immunohistochemical and gene expression assays. Results: When... (More)
Background: It is widely accepted that chronic inflammatory bowel diseases significantly higher a risk for colorectal cancer development. Among different types of treatments for patients with colon cancer, novel protein-based therapeutic strategies are considered. AIM: To explore the effect of human plasma alpha-1 antitrypsin (AAT) protein in the chemically induced mouse model of colorectal cancer. Methods: BALB/c mice with azoxymethane/dextran sodium sulfate (AOM/DSS)-induced colitis-associated colorectal cancer (CAC), we intraperitoneally treated with commercial preparation of human plasma AAT (4 mg per mouse). Effects of this therapy were evaluated histologically, and by immunohistochemical and gene expression assays. Results: When compared with non-treated controls, AOM/DSS mice receiving AAT therapy exhibited significantly longer colons, and less anal bleeding. Concurrently, AAT-treated mice had significantly fewer polyps, and lower numbers of large colon tumors. Immunohistochemical examinations of colon tissues showed significantly lower neutrophil counts, more granzyme B-positive but fewer MMP9 (gelatinase B)-positive cancer cells and lower numbers of apoptotic cells in mice receiving AAT therapy. The expression levels of IL4 were significantly higher while TNFA was slightly reduced in tumor tissues of AOM/DSS mice treated with AAT than in AOM/DSS mice. Conclusion: Human AAT is an acute phase protein with a broad-protease inhibitory and immunomodulatory activities used as a therapeutic for emphysema patients with inherited AAT deficiency. Our results are consistent with previous findings and support an idea that AAT alone and/or in combination with available anti-cancer therapies may represent a new personalized approach for patients with colitis-induced colon cancer.
(Less)
- author
- Al-Omari, Mariam ; Al-Omari, Tareq ; Batainah, Nesreen ; Al-Qauod, Khaled ; Olejnicka, Beata LU and Janciauskiene, Sabina LU
- organization
- publishing date
- 2023-12
- type
- Contribution to journal
- publication status
- published
- subject
- keywords
- Alpha1-antitrypsin, Caspase-3, Colorectal cancer, Cytokines, Granzyme-B, Inflammation, Matrix metalloproteinases, Mice model, Neutrophils
- in
- BMC Cancer
- volume
- 23
- issue
- 1
- article number
- 722
- publisher
- BioMed Central (BMC)
- external identifiers
-
- pmid:37532996
- scopus:85166406054
- ISSN
- 1471-2407
- DOI
- 10.1186/s12885-023-11195-5
- language
- English
- LU publication?
- yes
- id
- 91097b12-2bfa-444c-81e2-6813b2a02270
- date added to LUP
- 2023-10-19 09:35:14
- date last changed
- 2024-04-19 02:33:17
@article{91097b12-2bfa-444c-81e2-6813b2a02270,
abstract = {{<p>Background: It is widely accepted that chronic inflammatory bowel diseases significantly higher a risk for colorectal cancer development. Among different types of treatments for patients with colon cancer, novel protein-based therapeutic strategies are considered. AIM: To explore the effect of human plasma alpha-1 antitrypsin (AAT) protein in the chemically induced mouse model of colorectal cancer. Methods: BALB/c mice with azoxymethane/dextran sodium sulfate (AOM/DSS)-induced colitis-associated colorectal cancer (CAC), we intraperitoneally treated with commercial preparation of human plasma AAT (4 mg per mouse). Effects of this therapy were evaluated histologically, and by immunohistochemical and gene expression assays. Results: When compared with non-treated controls, AOM/DSS mice receiving AAT therapy exhibited significantly longer colons, and less anal bleeding. Concurrently, AAT-treated mice had significantly fewer polyps, and lower numbers of large colon tumors. Immunohistochemical examinations of colon tissues showed significantly lower neutrophil counts, more granzyme B-positive but fewer MMP9 (gelatinase B)-positive cancer cells and lower numbers of apoptotic cells in mice receiving AAT therapy. The expression levels of IL4 were significantly higher while TNFA was slightly reduced in tumor tissues of AOM/DSS mice treated with AAT than in AOM/DSS mice. Conclusion: Human AAT is an acute phase protein with a broad-protease inhibitory and immunomodulatory activities used as a therapeutic for emphysema patients with inherited AAT deficiency. Our results are consistent with previous findings and support an idea that AAT alone and/or in combination with available anti-cancer therapies may represent a new personalized approach for patients with colitis-induced colon cancer.</p>}},
author = {{Al-Omari, Mariam and Al-Omari, Tareq and Batainah, Nesreen and Al-Qauod, Khaled and Olejnicka, Beata and Janciauskiene, Sabina}},
issn = {{1471-2407}},
keywords = {{Alpha1-antitrypsin; Caspase-3; Colorectal cancer; Cytokines; Granzyme-B; Inflammation; Matrix metalloproteinases; Mice model; Neutrophils}},
language = {{eng}},
number = {{1}},
publisher = {{BioMed Central (BMC)}},
series = {{BMC Cancer}},
title = {{Beneficial effects of alpha-1 antitrypsin therapy in a mouse model of colitis-associated colon cancer}},
url = {{http://dx.doi.org/10.1186/s12885-023-11195-5}},
doi = {{10.1186/s12885-023-11195-5}},
volume = {{23}},
year = {{2023}},
}