1Medical Convergence Materials Commercialization Center, Gyeongsan

JaeJin An; Eun-Mi Ha

doi:10.1007/s12275-020-0375-y

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1Medical Convergence Materials Commercialization Center, Gyeongsan: JaeJin An ¹, Eun-Mi Ha ²; Journal of Microbiology 2020;58(11):967-977.
DOI: https://doi.org/10.1007/s12275-020-0375-y
Published online: October 30, 2020

¹Medical Convergence Materials Commercialization Center, Gyeongsan 38408, Republic of Korea, ²Department of Pharmacology, College of Pharmacy, Catholic University of Daegu, Gyeongsan 38430, Republic of Korea

Corresponding author: Eun-Mi Ha , Tel: +82-53-850-3612,

Received: 16 July 2020 • Revised: 7 September 2020 • Accepted: 15 September 2020

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Abstract

Lactobacillus plantarum-derived metabolites (LDMs) increase drug sensitivity to 5-FU and antimetastatic effects in 5-FUresistant 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.

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

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1Medical Convergence Materials Commercialization Center, Gyeongsan

J. Microbiol. 2020;58(11):967-977. Published online October 30, 2020

DOI: https://doi.org/10.1007/s12275-020-0375-y

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