The Combination Therapy of Fluorouracil and Oxaliplatin Suppress the Progression of Colon Cancer Through miR-183-5p/SOCS3 Axis and Downregulating PD-L1.
PD-L1
SOCS3
colon cancer
combination therapy
miR-183-5p
Journal
Cancer management and research
ISSN: 1179-1322
Titre abrégé: Cancer Manag Res
Pays: New Zealand
ID NLM: 101512700
Informations de publication
Date de publication:
2021
2021
Historique:
received:
15
09
2020
accepted:
20
01
2021
entrez:
4
3
2021
pubmed:
5
3
2021
medline:
5
3
2021
Statut:
epublish
Résumé
The purpose of this study was to investigate the mechanism of combination of fluorouracil (FU) and oxaliplatin (OXA) on the progression of colon cancer via miR-183-5p/SOCS3 axis and regulating PD-L1. HCT116 cells were treated with 4 μM OXA and 10.5 μM FU, or exogenous regulation of the expression of miR-183-5p, SOCS3 and PD-L1 in HCT116 cells. CCK-8 assay was employed to detect cell viability of HCT116 cells. Flow cytometry was performed to assess the apoptosis and cell cycle. The expression level of SOCS3, PD-L1, chemokines (CCL1, CCL4 and CCL7) and immune escapes related proteins (EGFR, STARD1 and STARD3) in HCT116 cells were assessed by Western blotting. In addition, dual-luciferase reporter gene was carried out to verify the targeted relationship between miR-183-5p with SOCS3. Our study demonstrated that the combination of OXA and FU remarkably suppressed proliferation, promoted apoptosis and arrest cells in G0/G1 phrase of HCT116 cells, and observably downregulated the expression of PD-L1, CCL1, CCL4, CCL7, EGFR, STARD1 and STARD3. Meanwhile, the combination of OXA and FU significantly downregulated miR-183-5p expression. Knockdown of miR-183-5p also repressed the proliferation, promoted apoptosis and arrest cells in G0/G1 phrase of HCT116 cells, and downregulated the expression of PD-L1, CCL1, CCL4, CCL7, EGFR, STARD1 and STARD3. In addition, our study proved that miR-183-5p upregulated PD-L1 by targeting downregulated SOCS3 expression. Finally, we demonstrated that the combination therapy of OXA and FU inhibited the proliferation, promote apoptosis and arrest cells in G0/G1 phrase by downregulating PD-L1 via miR-183-5p/SOCS3 axis. The combination therapy of OXA and FU could suppress the malignant biological behavior, and the mechanism was realized by inhibiting PD-L1 through miR-183-5p/SOCS3 axis.
Identifiants
pubmed: 33658858
doi: 10.2147/CMAR.S281925
pii: 281925
pmc: PMC7920511
doi:
Types de publication
Journal Article
Langues
eng
Pagination
1999-2008Informations de copyright
© 2021 Tu et al.
Déclaration de conflit d'intérêts
The authors report no conflicts of interest in this work.
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