LDLR promotes autophagy-mediated cisplatin resistance in ovarian cancer associated with the PI3K/AKT/mTOR signaling pathway.
Kaohsiung J Med Sci
; 39(8): 779-788, 2023 Aug.
Article
en En
| MEDLINE
| ID: mdl-37218642
ABSTRACT
Autophagy is one of the underlying causes of resistance to many antitumor drugs, including cisplatin (DDP). The low-density lipoprotein receptor (LDLR) is a regulator of ovarian cancer (OC) progression. However, whether LDLR regulates DDP resistance in OC via autophagy-related pathways remains unclear. LDLR expression was measured by quantitative real-time PCR, western blot (WB) and IHC staining. A Cell Counting Kit 8 assay was employed to evaluate DDP resistance and cell viability, and flow cytometry was used to assess apoptosis. WB analysis was employed to evaluate the expression of autophagy-related proteins and PI3K/AKT/mTOR signaling pathway proteins. The autophagolysosomes and the fluorescence intensity of LC3 were observed by transmission electron microscopy and immunofluorescence staining, respectively. A xenograft tumor model was established to explore the role of LDLR in vivo. LDLR was highly expressed in OC cells, which was correlated with disease progression. In DDP-resistant OC cells, high LDLR expression was related to DDP resistance and autophagy. Downregulation of LDLR repressed autophagy and growth in DDP-resistant OC cell lines by activating the PI3K/AKT/mTOR pathway, and these effects were eliminated by an mTOR inhibitor. In addition, LDLR knockdown also reduced OC tumor growth by suppressing autophagy associated with the PI3K/AKT/mTOR pathway. LDLR promoted autophagy-mediated DDP resistance in OC associated with the PI3K/AKT/mTOR pathway, indicating that LDLR might be a new target to prevent DDP resistance in OC patients.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Neoplasias Ováricas
/
Receptores de LDL
/
Cisplatino
Tipo de estudio:
Risk_factors_studies
Límite:
Animals
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Female
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Humans
Idioma:
En
Revista:
Kaohsiung J Med Sci
Asunto de la revista:
MEDICINA
Año:
2023
Tipo del documento:
Article