Retinoids Decrease Soluble MICA Concentration by Inhibiting the Enzymatic Activity of ADAM9 and ADAM10.
Anticancer Res
; 41(5): 2307-2320, 2021 May.
Article
em En
| MEDLINE
| ID: mdl-33952456
ABSTRACT
BACKGROUND/AIM:
The association between MHC class I polypeptide-related sequence A (MICA) and hepatocellular carcinoma (HCC) development was identified in our previous genome-wide association study. Decreasing soluble MICA (sMICA) through MICA sheddases suppression facilitates natural killer (NK) cell-mediated cytotoxicity. The expression of ADAM9 in HCC has been correlated with poor prognosis, and our recent study showed that its suppression contributes to cancer elimination by decreasing sMICA. MATERIALS ANDMETHODS:
Human HCC cell line PLC/PRF/5 and HepG2 cells were used. sMICA levels were measured by ELISA. Expression of retinoid X receptors (RXRs) and retinoic acid receptors (RARs) was knocked down by siRNA.RESULTS:
In our screening of FDA-approved drugs in vitro, retinoids were found to be efficient ADAM9 and ADAM10 inhibitors. Treatment with retinoids reduced sMICA levels in human HCC cells. Interestingly, the effects were abrogated by depletion of the retinoid receptor RXRα.CONCLUSION:
Retinoids can be potential novel agents for HCC treatment.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Retinoides
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Antígenos de Histocompatibilidade Classe I
/
Proteínas ADAM
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Proteína ADAM10
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Proteínas de Membrana
Limite:
Humans
Idioma:
En
Revista:
Anticancer Res
Ano de publicação:
2021
Tipo de documento:
Article