Sunitinib induced resistance of endothelial cells by up-regulating P-glycoprotein and PI3K/Akt pathway
Document title: Sunitinib induced resistance of endothelial cells by up-regulating P-glycoprotein and PI3K/Akt pathway
Journal: Brazilian Journal of Pharmaceutical Sciences
Database: PERIÓDICA
System number: 000451785
ISSN: 1984-8250
Authors: 1
2
1
1
Institutions: 1Guizhou Medical University, School of Pharmaceutical Sciences, Guian New District, Guizhou. China
2People’s Hospital of Guizhou Province, Department of Oncology, Guian New District, Guizhou. China
Year:
Volumen: 58
Country: Brasil
Language: Inglés
Document type: Artículo
Approach: Experimental, aplicado
English abstract Drug resistance is a crucial obstacle to achieve satisfactory chemotherapeutic effects. Numerous studies have shown that the PI3K/Akt signaling pathway plays a significant role in various processes of cellular events and tumor progression, while few studies have focused on the PI3K/Akt signaling pathway in drug resistance of endothelial cells. The present study aims to explore the relationship of PI3K/Akt signaling and cellular resistance to anticancer drugs in human microvessel endothelial cells (HMEC-1). We established stable sunitinib-resiatant human microvessel endothelial cells (HMEC-su) after long-term exposure to sunitinib (a small-molecule tyrosine kinase receptor inhibitor) for 12 months. HMEC-su showed significant alternations of cell morphology and exhibited a 2.32-fold higher IC50 of sunitinib than parental HMEC-1 cells. Expression of P-glycoprotein (P-gp) and breast cancer-resistance protein (ABCG2) which mediates drug efflux, increased significantly in HMEC-su lines compared with HMEC-1 cells by western blots assay. Our study further demonstrates that LY294002 (blocking the PI3K/Akt pathway) enhances the sensibility of HMEC-su to suntinib and inhibits the gene transcription and protein expression of P-gp, ABCG2 in HMEC-su cells. In conclusion, these results indicate that LY294002 could reverse P-gp and ABCG2 mediated-drug resistance to sunitinib in HMEC-su cells by inhibiting PI3K/Akt signaling
Disciplines: Medicina,
Química
Keyword: Oncología,
Farmacología,
Antineoplásicos,
Células endoteliales,
Resistencia a fármacos,
P-glucoproteína,
Sunitinib
Keyword: Oncology,
Pharmacology,
Antineoplastic agents,
Drug resistance,
Endothelial cells,
P-glycoprotein,
Sunitinib
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