Identification of an m6A Natural Inhibitor, Lobeline, That Reverses Lenvatinib Resistance in Hepatocellular Tumors.
J Nat Prod
; 87(8): 1983-1993, 2024 Aug 23.
Article
em En
| MEDLINE
| ID: mdl-39136667
ABSTRACT
Hepatocellular carcinoma (HCC) is an aggressive cancer that has an effect on human health. As a first-line drug for HCC, despite its excellent efficacy, lenvatinib (Len) is prone to developing drug resistance in HCC patients. The N6-methyladenosine (m6A) modification is not only related to the development of HCC but also shows great potential in overcoming HCC resistance. Using Dot Blot, our group first screened a small molecule m6A regulator, lobeline (Lob), from a library of 390 compounds (mostly natural products). In vitro experiments demonstrated that Lob could significantly enhance the sensitivity to Len of Len-resistant HCC (HCC/Len) and inhibit migration of resistant cells. In Len-resistant cell-derived and patient-derived xenograft models, Lob could reverse the resistant phenotype, with reductions in tumor volume of 68% and 60%, respectively. Furthermore, MeRIP-m6A sequencing results indicated that the underlying molecular mechanism of Lob reversal of HCC drug resistance was related to UBE3B. Taken together, this study highlighted that Lob, a plant derived natural product, could reverse the resistance of HCC to Len by regulating the m6A levels. It is hoped that this will provide a pharmacological research basis for the clinical treatment of HCC patients.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Compostos de Fenilureia
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Quinolinas
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Carcinoma Hepatocelular
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Resistencia a Medicamentos Antineoplásicos
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Neoplasias Hepáticas
Limite:
Animals
/
Humans
Idioma:
En
Revista:
J Nat Prod
Ano de publicação:
2024
Tipo de documento:
Article
País de afiliação:
China
País de publicação:
Estados Unidos