SOD2 confers anlotinib resistance via regulation of mitochondrial damage in OSCC.
Oral Dis
; 2022 Oct 13.
Article
en En
| MEDLINE
| ID: mdl-36229195
ABSTRACT
OBJECTIVE:
Previous studies had revealed that anlotinib had outstanding anti-tumor efficacy on oral squamous cell carcinoma. However, the underlying mechanism is still unclear. MATERIALS ANDMETHODS:
Anlotinib resistant OSCC cells were established and analyzed by RNA-sequencing. The correlations between SOD2 expression and anlotinib resistance were investigated in OSCC cells and PDX models. Functional assays were performed to verify the SOD2 expression and anlotinib resistance in OSCC cells.RESULTS:
Anlotinib resistant genes were enriched in the biological processes of mitochondrion organization and the gene pathway of reactive oxygen species. SOD2 expression level was positively correlated with the resistance of anlotinib in OSCC cells and PDX models. Higher SOD2 expression of OSCC cells was more resistant to anlotinib. Anlotinib induced ROS generation, apoptosis and mitochondrial damage in OSCC cells, which can be enhanced by SOD2 knockdown and decreased by SOD2 overexpression. Mitochondrial damage was identified as swelling and cristae disappearance morphology under TEM, decreased mitochondrial membrane potential and lower MFN2 expression.CONCLUSIONS:
SOD2 may be capable of protecting mitochondria by downregulating ROS generation, which contributes to the resistance of anlotinib in OSCC cells. SOD2 can be utilized as a potential therapeutic target to improve the anti-cancer efficacy of anlotinib in OSCC.
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Idioma:
En
Revista:
Oral Dis
Asunto de la revista:
ODONTOLOGIA
Año:
2022
Tipo del documento:
Article
País de afiliación:
China