Abstract
Probiotics are known to be a potential agent for colorectal cancer (CRC) inhibition, but the precise mechanisms by which probiotic exert anti-tumorigenic effects remain to be explored. Lactobacillus salivarius (LS) Ren was isolated from centenarians living in Bama of China, which showed an anticancer potent in animal model of oral cancer. Here, we investigated the effect of LS on colorectal carcinogenesis and its putative mechanism. Oral administration of LS effectively suppressed the formation of dimethylhydrazine (DMH)-induced CRC in both initial and post-initial stages. Significant antiproliferation and proapoptotic effects were observed with inhibition of tumor formation by dietary intake of LS. Besides, LS metabolites inhibited growth, arrested cell cycle, and induced apoptosis of HT-29 cells. Furthermore, upon the treatment of LS, protein kinase B (AKT) phosphorylation and the downstream proteins of cyclinD1 and cyclooxygenase-2 (COX-2) were significantly downregulated in both in vivo and in vitro tests. These results showed that LS inhibited the colorectal carcinogenesis through suppressing AKT signaling pathway, resulting in suppressing cell proliferation and inducing cell apoptosis. Our findings suggest that this probiotic may act as a prophylactic agent for CRC prevention.
Key points • LS effectively prevented rat colorectal carcinogenesis induced by DMH. • LS modulated the proliferation and apoptosis in both in vivo and in vitro. • LS inhibited AKT phosphorylation and expressions of downstream cyclinD1 and COX-2. |
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Funding
This work was funded by the National Key Research and Development Program of China (grant number: 2018YFD0400305), National Natural Science Foundation of China (grant number: 31601443), Project of High-Level Teachers in Beijing Municipal Universities in the Period of 13th Five-Year Plan (grant number: CIT&TCD201804022), and Scientific Research Project of Beijing Municipal Education Commission (grant number: KZ201910011014).
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Data curation, Yuanyuan Dong; formal analysis, Jun Zhu; funding acquisition, Ming Zhang and Liang Zhao; investigation, Jun Zhu, Shaoyang Ge, and Liang Zhao; methodology, Yuanyuan Dong; project administration, Yuanyuan Dong, Jun Zhu, Ming Zhang, and Liang Zhao; resources, Shaoyang Ge; supervision, Ming Zhang; and writing (original draft), Ming Zhang.
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All protocols and procedures of animal handling during the experiment were strictly followed by the guidelines of the State Standard of the People’s Republic of China of laboratory animal (GB 14925) and the European Communities Council Directive (2010/63/EU) and were approved by the Laboratory Animal Welfare and Animal Experimental Ethical Committee of China Agricultural University (CAU20180220–5).
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Dong, Y., Zhu, J., Zhang, M. et al. Probiotic Lactobacillus salivarius Ren prevent dimethylhydrazine-induced colorectal cancer through protein kinase B inhibition. Appl Microbiol Biotechnol 104, 7377–7389 (2020). https://doi.org/10.1007/s00253-020-10775-w
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DOI: https://doi.org/10.1007/s00253-020-10775-w