Polydatin, a potential NOX5 agonist, synergistically enhances antitumor activity of cisplatin by stimulating oxidative stress in nonsmall cell lung cancer.
Int J Oncol
; 65(2)2024 Aug.
Article
en En
| MEDLINE
| ID: mdl-38873997
ABSTRACT
Nonsmall cell lung cancer (NSCLC) is one of the major causes of cancerrelated death worldwide. Cisplatin is a frontline chemotherapeutic agent in NSCLC. Nevertheless, subsequent harsh side effects and drug resistance limit its further clinical application. Polydatin (PD) induces apoptosis in various cancer cells by generating reactive oxygen species (ROS). However, underlying molecular mechanisms of PD and its effects on cisplatinmediated antitumor activity in NSCLC remains unknown. MTT, colony formation, wound healing analyses and flow cytometry was employed to investigate the cell phenotypic changes and ROS generation. Relative gene and protein expressions were evaluated by reverse transcriptionquantitative PCR and western blot analyses. The antitumor effects of PD, cisplatin and their combination were evaluated by mouse xenograft model. In the present study, it was found that PD in combination with cisplatin synergistically enhances the antitumor activity in NSCLC by stimulating ROSmediated endoplasmic reticulum stress, and the CJunaminoterminal kinase and p38 mitogenactivated protein kinase signaling pathways. PD treatment elevated ROS generation by promoting expression of NADPH oxidase 5 (NOX5), and NOX5 knockdown attenuated ROSmediated cytotoxicity of PD in NSCLC cells. Mice xenograft model further confirmed the synergistic antitumor efficacy of combined therapy with PD and cisplatin. The present study exhibited a superior therapeutic strategy for some patients with NSCLC by combining PD and cisplatin.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Estilbenos
/
Cisplatino
/
Especies Reactivas de Oxígeno
/
Carcinoma de Pulmón de Células no Pequeñas
/
Estrés Oxidativo
/
Ensayos Antitumor por Modelo de Xenoinjerto
/
Sinergismo Farmacológico
/
NADPH Oxidasa 5
/
Glucósidos
/
Neoplasias Pulmonares
Límite:
Animals
/
Humans
/
Male
Idioma:
En
Revista:
Int J Oncol
Asunto de la revista:
NEOPLASIAS
Año:
2024
Tipo del documento:
Article