Effects of Alpha-Connexin Carboxyl-Terminal Peptide (aCT1) and Bowman-Birk Protease Inhibitor (BBI) on Canine Oral Mucosal Melanoma (OMM) Cells.
Effects of Alpha-Connexin Carboxyl-Terminal Peptide (aCT1) and Bowman-Birk Protease Inhibitor (BBI) on Canine Oral Mucosal Melanoma (OMM) Cells.
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DOI：
10.3389/fvets.2021.670451
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发表时间：
2021
影响因子：
3.2
通讯作者：
Dagli MLZ
中科院分区：
文献类型：
--
作者：
Sato A;da Fonseca IIM;Nagamine MK;de Toledo GF;Olio R;Hernandez-Blazquez FJ;Yano T;Yeh ES;Dagli MLZ
口腔黏膜黑色素瘤（OMM）是犬的侵袭性癌症，也是人类OMM的良好模型。间隙连接由连接蛋白单位组成，它可能改变了癌细胞的表达模式和/或亚细胞定位。在包括黑色素瘤在内的癌细胞中，细胞间通过间隙连接的通讯经常受损。同时，缝隙连接蛋白连接蛋白43 （Cx43）的上调表达抑制黑色素瘤的进展。据报道，α-连接蛋白羧基末端（aCT1）肽在人乳腺细胞中维持Cx43的表达和细胞间的通讯，并通过功能试验增加了通过间隙连接的通讯活性，从而导致细胞增殖下降。Bowman-Birk蛋白酶抑制剂（BBI）是大豆的一种成分，在几种肿瘤细胞中诱导Cx43表达，具有胰蛋白酶-凝乳胰蛋白酶抑制功能，具有抗肿瘤作用。本研究探讨了aCT1肽和BBI单独或联合治疗对TLM1犬黑色素瘤细胞活力的影响。用PrestoBlue法分析aCT1、逆序肽（R-pep）和/或BBI处理5天后的细胞活力。免疫荧光法观察Cx43的定位和表达。单独使用aCT1 （200 μM）对TLM1细胞活力无显著影响，而单独使用BBI （400 μg/ml）对TLM1细胞活力有显著影响。aCT1 （200 μM）和BBI （400 μg/ml）联合处理可显著降低TLM1细胞活力。经免疫染色检测，TLM1细胞中Cx43的表达在BBI和aCT1联合作用后，细胞膜中表达增加。这种双重处理可以联合起来实现抗癌活性，可能是通过增加Cx43的表达和影响Cx43向细胞膜的迁移。总之，利用BBI和aCT1靶向Cx43的治疗策略可能会为犬OMM带来新的有效治疗方法。
Oral mucosal melanomas (OMM) are aggressive cancers in dogs, and are good models for human OMM. Gap junctions are composed of connexin units, which may have altered expression patterns and/or subcellular localization in cancer cells. Cell-to-cell communication by gap junctions is often impaired in cancer cells, including in melanomas. Meanwhile, the upregulated expression of the gap junction protein connexin 43 (Cx43) inhibits melanoma progression. The α-connexin carboxyl-terminal (aCT1) peptide reportedly maintains Cx43 expression and cell-cell communication in human mammary cells and increases the communication activity through gap junctions in functional assays, therefore causing decreased cell proliferation. The Bowman-Birk protease inhibitor (BBI), a component of soybeans, induces Cx43 expression in several tumor cells as a trypsin–chymotrypsin inhibition function, with antineoplastic effects. This study investigated the effect of aCT1 peptide and BBI treatment, alone or in combination, on TLM1 canine melanoma cell viability. Cell viability after treatment with aCT1, the reverse sequence peptide (R-pep), and/or BBI for 5 days was analyzed by PrestoBlue assay. Immunofluorescence was used to observe Cx43 localization and expression. aCT1 (200 μM) alone did not significantly decrease cell viability in TLM1 cells, whereas BBI (400 μg/ml) alone significantly decreased the TLM1 viability. Combined treatment with both aCT1 (200 μM) and BBI (400 μg/ml) significantly decreased cell viability in TLM1 cells. Cx43 expression, as identified by immunostainings in TLM1 cells, was increased in the cell membrane after the combination treatment with BBI and aCT1. This dual treatment can be combined to achieve the anticancer activity, possibly by increasing Cx 43 expression and affecting Cx43 migration to the cell membrane. In conclusion, a treatment strategy targeting Cx43 with BBI and aCT1 may possibly lead to new effective therapies for canine OMM.
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影响因子：
6.4
作者：
Kou, Yu;Ji, Liyan;Lu, Linlin
通讯作者：
Lu, Linlin
DOI：
10.1053/j.ctsap.2007.03.004
发表时间：
2007-05-01
期刊：
CLINICAL TECHNIQUES IN SMALL ANIMAL PRACTICE
影响因子：
--
作者：
Bergman, Philip J.
通讯作者：
Bergman, Philip J.
影响因子：
2.4
作者：
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通讯作者：
MATUS, R
影响因子：
5.6
作者：
Graham SV;Jiang JX;Mesnil M
通讯作者：
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影响因子：
5.6
作者：
Nalewajska M;Marchelek-Myśliwiec M;Opara-Bajerowicz M;Dziedziejko V;Pawlik A
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Pawlik A