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
| Autor: | JaeJin An, Eun Mi Ha |
|---|---|
| Rok vydání: | 2020 |
| Předmět: |
Antimetabolites
Antineoplastic Combination therapy Colorectal cancer Applied Microbiology and Biotechnology Microbiology Metastasis 03 medical and health sciences Downregulation and upregulation Claudin-1 medicine Gene silencing Humans Claudin 030304 developmental biology 0303 health sciences 030306 microbiology Cell growth Chemistry Probiotics General Medicine medicine.disease HCT116 Cells Drug Resistance Neoplasm Paracellular transport Cancer research Drug Therapy Combination Fluorouracil Colorectal Neoplasms Lactobacillus plantarum |
| Zdroj: | Journal of microbiology (Seoul, Korea). 58(11) |
| ISSN: | 1976-3794 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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