Supramolecular nanodrug targeting CDK4/6 overcomes BAG1 mediated cisplatin resistance in oral squamous cell carcinoma.
J Control Release
; 368: 623-636, 2024 Apr.
Article
de En
| MEDLINE
| ID: mdl-38479445
ABSTRACT
Chemoresistance to cisplatin remains a significant challenge affecting the prognosis of advanced oral squamous cell carcinoma (OSCC). However, the specific biomarkers and underlying mechanisms responsible for cisplatin resistance remain elusive. Through comprehensive bioinformatic analyses, we identified a potential biomarker, BCL2 associated athanogene-1 (BAG1), showing elevated expression in head and neck squamous cell carcinoma (HNSCC). Since OSCC represents the primary pathological type of HNSCC, we investigated BAG1 expression in human tumor tissues and cisplatin resistant OSCC cell lines, revealing that silencing BAG1 induced apoptosis in cisplatin-resistant cells both in vitro and in vivo. This effect led to impaired cell viability of cisplatin resistant OSCC cells and indicated a positive correlation between BAG1 expression and the G1/S transition during cell proliferation. Based on these insights, the administration of a CDK4/6 inhibitor in combination with cisplatin effectively overcame cisplatin resistance in OSCC through the CDK4/6-BAG1 axis. Additionally, to enable simultaneous drug delivery and enhance synergistic antitumor efficacy, we developed a novel supramolecular nanodrug LEE011-FFERGD/CDDP, which was validated in an OSCC orthotopic mouse model. In summary, our study highlights the potential of a combined administration of CDK4/6 inhibitor and cisplatin as a promising therapeutic regimen for treating advanced or cisplatin resistant OSCC.
Mots clés
Texte intégral:
1
Collection:
01-internacional
Base de données:
MEDLINE
Sujet principal:
Tumeurs de la bouche
/
Carcinome épidermoïde
/
Résistance aux médicaments antinéoplasiques
/
Kinase-4 cycline-dépendante
/
Kinase-6 cycline-dépendante
/
Nanoparticules
Limites:
Animals
/
Humans
Langue:
En
Journal:
J Control Release
Sujet du journal:
FARMACOLOGIA
Année:
2024
Type de document:
Article
Pays d'affiliation:
Chine