LyeTx I-b Peptide Attenuates Tumor Burden and Metastasis in a Mouse 4T1 Breast Cancer Model

被引:16
作者
Abdel-Salam, Mostafa A. L. [1 ]
Pinto, Barbara [1 ]
Cassali, Geovanni [2 ]
Bueno, Lilian [3 ]
Pegas, Gabriela [2 ]
Oliveira, Fabricio [2 ]
Silva, Irismara [4 ]
Klein, Andre [4 ]
de Souza-Fagundes, Elaine Maria [1 ]
de Lima, Maria Elena [5 ]
Carvalho-Tavares, Juliana [1 ]
机构
[1] Univ Fed Minas Gerais, Inst Ciencias Biol, Dept Fisiol & Biofis, Programa Posgrad Ciencias Biol Fisiol & Farmacol, BR-31270901 Belo Horizonte, MG, Brazil
[2] Univ Fed Minas Gerais, Inst Ciencias Biol, Dept Patol Geral, BR-31270901 Belo Horizonte, MG, Brazil
[3] Univ Fed Minas Gerais, Inst Ciencias Biol, Dept Parasitol, BR-31270901 Belo Horizonte, MG, Brazil
[4] Univ Fed Minas Gerais, Inst Ciencias Biol, Dept Farmacol, Programa Posgrad Ciencias Biol Fisiol & Farmacol, BR-31270901 Belo Horizonte, MG, Brazil
[5] Fac Santa Casa Belo Horizonte, Programa Posgrad Med Biomed, BR-30110005 Belo Horizonte, MG, Brazil
来源
ANTIBIOTICS-BASEL | 2021年 / 10卷 / 09期
关键词
breast cancer; LyeTx I-b peptide; immunomodulation; leukocyte recruitment; cytokines; anticancer activity of LyeTx I-b; Lycosa erythrognatha; ANTIMICROBIAL PEPTIDES; CHEMOTHERAPY; APOPTOSIS; INFLAMMATION; CARCINOMA; MIGRATION; EFFICACY; IMMUNITY; THERAPY; CELLS;
D O I
10.3390/antibiotics10091136
中图分类号
R51 [传染病];
学科分类号
100401 ;
摘要
Cationic anticancer peptides have exhibited potent anti-proliferative and anti-inflammatory effects in neoplastic illness conditions. LyeTx I-b is a synthetic peptide derived from Lycosa erythrognatha spider venom that previously showed antibiotic activity in vitro and in vivo. This study focused on the effects of LyeTxI-b on a 4T1 mouse mammary carcinoma model. Mice with a palpable tumor in the left flank were subcutaneously or intratumorally injected with LyeTx I-b (5 mg/kg), which significantly decreased the tumor volume and metastatic nodules. Histological analyses showed a large necrotic area in treated primary tumors compared to the control. LyeTxI-b reduced tumor growth and lung metastasis in the 4T1 mouse mammary carcinoma model with no signs of toxicity in healthy or cancerous mice. The mechanism of action of LyeTx I-b on the 4T1 mouse mammary carcinoma model was evaluated in vitro and is associated with induction of apoptosis and cell proliferation inhibition. Furthermore, LyeTx I-b seems to be an efficient regulator of the 4T1 tumor microenvironment by modulating several cytokines, such as TGF-beta, TNF-alpha, IL-1 beta, IL-6, and IL-10, in primary tumor and lung, spleen, and brain. LyeTx I-b also plays a role in leukocytes rolling and adhesion into spinal cord microcirculation and in the number of circulating leukocytes. These data suggest a potent antineoplastic efficacy ofLyeTx I-b.
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页数:28
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