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Lactobacillus-derived metabolites enhance the antitumor activity of 5-FU and inhibit metastatic behavior in 5-FU-resistant colorectal cancer cells by regulating claudin-1 expression

Journal of Microbiology 2020년 58권 11호 p.967 ~ 977
안재진, 하은미,
소속 상세정보
안재진 ( An Jae-Jin ) - Medical Convergence Materials Commercialization Center
하은미 ( Ha Eun-Mi ) - Catholic University of Daegu College of Pharmacy Department of Pharmacology

Abstract


Lactobacillus plantarum-derived metabolites (LDMs) increase drug sensitivity to 5-FU and antimetastatic effects in 5-FU-resistant colorectal cancer cells (HCT-116/5FUR). In this study, we evaluated the effects of LDMs on the regulation of genes and proteins involved in HCT-116/5-FUR cell proliferation and metastasis. HCT-116/5-FUR cells showed high metastatic potential, significantly reduced tight junction (TJ) integrity, including increased migration and paracellular permeability, and upregulation of claudin-1 (CLDN-1). The genetic silencing of CLDN-1 increased the sensitivity of HCT-116/5FUR to 5-FU and inhibited its metastatic potential by regulating the expression of epithelial-mesenchymal transition (EMT) related genes. Co-treatment of HCT-116/5FUR with LDMs and 5-FU suppressed chemoresistant and metastatic behavior by downregulating CLDN-1 expression. Finally, we designed LDMs-based therapeutic strategies to treatment for metastatic 5-FU-resistant colorectal cancer cells. These results suggested that LDMs and 5-FU cotreatments can synergistically target 5-FU-resistant cells, making it a candidate strategy to overcome 5-FU chemoresistance improve anticancer drug efficacy.

키워드

colorectal cancer; HCT-116; 5-FU; chemoresistant; Lactobacillus; metastasis; tight junction; CLDN-1; combination therapy

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