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.
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