Exosomes Mediate the Production of Oxaliplatin Resistance and Affect Biological Behaviors of Colon Cancer Cell Lines.
Curr Cancer Drug Targets
; 2024 Jul 02.
Article
em En
| MEDLINE
| ID: mdl-38956907
ABSTRACT
BACKGROUND:
Colon cancer has high mortality rate which making it one of the leading causes of cancer deaths. Oxaliplatin is a common chemotherapeutic drug, but it has disadvantages such as drug resistance.OBJECTIVE:
The purpose of this study is to explore the mechanism of exosomes in the resistance of oxaliplatin and verify whether elemene and STAT3 inhibitors reverse the resistance to oxaliplatin.METHODS:
Related cell line models were constructed and the proliferation, migration, invasion, apoptosis and resistance to oxaliplatin were evaluated for all three cells of HCT116/L, sensitive cell HCT116 and HCT116+HCT116/L-exosomes (HCT116-exo). It was to explore probable signaling pathways and mechanisms by Western blotting.RESULTS:
HCT116-exo drug-resistant chimeric cells showed greater capacity for proliferation, migration and invasion than HCT116 sensitive cells. After the above cells were treated with oxaliplatin, the apoptosis rate of chimeric drug-resistant cells HCT116-exo and its IC50 increased compared with the sensitive cells HCT116. The proliferation, invasion and migration of cells treated with STAT3 inhibitor or ß-elemene combined with oxaliplatin reduced compared with those treated with oxaliplatin or ß-elemene alone. The STAT3 inhibitor or ß-elemene in combination with oxaliplatin increased the rate of apoptosis relative to oxaliplatin or ß-elemene alone. Drug-resistant cell exosomes could promote the EMT process, related to the participation of FGFR4, SHMT2 and STAT3 inhibitors.CONCLUSION:
Drug-resistant cell exosomes could induce resistance, and improve the capacity of colon cancer towards proliferate, invade, migrate and promote the EMT process. The ß-elemene combined with oxaliplatin could reverse the above results which might be related to the STAT3 pathway and EMT pathway in colon cancer.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Idioma:
En
Revista:
Curr Cancer Drug Targets
Ano de publicação:
2024
Tipo de documento:
Article