Argyris Dimitrios G, Markaki Maria P, Afaloniati Hara, Karagiannis George S, Poutahidis Theofilos, Angelopoulou Katerina
Laboratory of Biochemistry and Toxicology, School of Veterinary Medicine, Faculty of Health Sciences, Aristotle University of Thessaloniki, Thessaloniki, Greece.
Department of Microbiology and Immunology, Albert Einstein College of Medicine, Bronx, NY, USA.
Mol Biol Rep. 2025 Jan 22;52(1):150. doi: 10.1007/s11033-025-10271-2.
Lately, significant attention has been drawn towards the potential efficacy of cholera toxin (CT)-an exotoxin produced by the small intestine pathogenic bacterium Vibrio cholera-in modulating cancer-promoting events. In a recent study, we demonstrated that early-life oral administration of non-pathogenic doses of CT in mice suppressed chemically-induced carcinogenesis in tissues distantly located from the gut. In the mammary gland, CT pretreatment was shown to reduce tumor multiplicity, increase apoptosis and alter the expression of several cancer-related molecules. In the present work we investigated the protumorigenic mammary microenvironment for possible associations between early life CT administration and the expression of key components of the Bmp and Notch signaling pathways.
Total RNA from mammary tissue samples were retrieved from a recent experiment where FVB/N female mice were preconditioned with CT and later treated with the carcinogen 7,12-dimethylbenzanthracene (DMBA). Real-time PCR was used for relative quantification of gene expression. Our results revealed that CT anti-tumor effects significantly correlated with deregulation of crucial BMP pathway elements, with downregulation of Bmp7 ligand and upregulation of inhibitory Smad6 being the most prominent alterations observed. Concerning Notch signaling pathway, significantly elevated gene expression levels in the CT-treated DMBA mice, as compared to their non-treated counterparts, were also identified at the ligand-receptor level.
These findings suggest that CT tumor protective effects in the mammary gland are associated with discerning deregulation of components of both Bmp and Notch signaling pathways and provide insights into the mechanisms underlying CT's anti-cancer outcome.
最近，霍乱毒素（CT）——一种由小肠致病细菌霍乱弧菌产生的外毒素——在调节癌症促进事件方面的潜在功效受到了极大关注。在最近的一项研究中，我们证明了在小鼠生命早期口服非致病剂量的CT可抑制远离肠道的组织中化学诱导的致癌作用。在乳腺中，CT预处理显示可减少肿瘤多发性、增加细胞凋亡并改变几种癌症相关分子的表达。在本研究中，我们调查了促肿瘤的乳腺微环境，以探究生命早期给予CT与Bmp和Notch信号通路关键成分表达之间可能存在的关联。
乳腺组织样本的总RNA取自最近一项实验，在该实验中，FVB/N雌性小鼠先用CT预处理，随后用致癌物7,12 - 二甲基苯并蒽（DMBA）处理。实时PCR用于基因表达的相对定量。我们的结果显示，CT的抗肿瘤作用与关键BMP通路元件的失调显著相关，其中Bmp7配体的下调和抑制性Smad6的上调是观察到的最显著变化。关于Notch信号通路，与未处理的小鼠相比，在CT处理的DMBA小鼠中，在配体 - 受体水平也发现基因表达水平显著升高。
这些发现表明，CT在乳腺中的肿瘤保护作用与Bmp和Notch信号通路成分的明显失调有关，并为CT抗癌结果的潜在机制提供了见解。
