Cargando…

Downregulation of HIF-2α Reverse the Chemotherapy Resistance of Lung Adenocarcinoma A549 Cells to Cisplatin

BACKGROUND: Cisplatin (DDP)-based systemic chemotherapy has been widely used in the treatment of postoperative or advanced NSCLC patients, however, its effective rate is only 14~40%. HIF-2α can upregulate drug-resistant-related genes expression and lead to chemotherapy resistance in many tumors. How...

Descripción completa

Detalles Bibliográficos
Autores principales: Gao, Zhao-jia, Yuan, Wei-dong, Yuan, Jun-qiang, Yuan, Kai, Wang, Yong
Formato: Online Artículo Texto
Lenguaje:English
Publicado: International Scientific Literature, Inc. 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5832106/
https://www.ncbi.nlm.nih.gov/pubmed/29469087
http://dx.doi.org/10.12659/MSM.906107
Descripción
Sumario:BACKGROUND: Cisplatin (DDP)-based systemic chemotherapy has been widely used in the treatment of postoperative or advanced NSCLC patients, however, its effective rate is only 14~40%. HIF-2α can upregulate drug-resistant-related genes expression and lead to chemotherapy resistance in many tumors. However, little is known about the relationship between HIF-2α and chemotherapy resistance of lung cancer cells. MATERIAL/METHODS: In our study, the siRNA expression vectors targeting the HIF-2α gene were designed, constructed, and transfected into A549 cells. MTT assay and western blot analysis of P-glycoprotein 1 (P-gp) were used to explore the transfer influence of HIF-2α gene silencing on the A549 cells in the cisplatin-based chemotherapy resistance. RESULTS: After transfection with the siRNA(HIF-2α) into A549 cells, mRNA and protein expression of HIF-2α were downregulated. At the same time, expression of P-gp decreased significantly. Furthermore, the sensitivity to cisplatin significantly increased. CONCLUSIONS: The constructed siRNA expression vectors can effectively suppress the expression of HIF-2α and P-gp, which then can reverse the chemotherapy resistance of A549 cells.