The Role of Angiogenesis in the Persistence of Chemoresistance in Epithelial Ovarian Cancer. (November 2016)

• Record Type: Journal Article
• Authors: Nusrat, Osama; Belotte, Jimmy; Fletcher, Nicole M.; Memaj, Ira; Saed, Mohammed G.; Diamond, Michael P.; Saed, Ghassan M.
• Is Part Of: Reproductive sciences. Volume 23:Number 11(2016:Nov.)
• Page Start: 1484
• Page End: 1492
• Publication Date: 2016-11
• Subjects: chemoresistance -- ovarian cancer -- vascular endothelial growth factor -- and hypoxia-inducible factor-1α; Reproductive health -- Periodicals; Reproduction -- Periodicals; 612.6
• DOI: 10.1177/1933719116645191
• Languages: English
• ISSNs: 1933-7191

Abstract

Objective: Chemoresistance remains a major challenge in the treatment of ovarian cancer. As part of a survival mechanism, tumor cells have been shown to release proangiogenic factors, such as vascular endothelial growth factor (VEGF), through a mechanism that involves the upregulation of hypoxia-induced factor (HIF)-1α. The objective of this study was to compare the expression of VEGF and its receptors (R1 and R2) as well as HIF-1α in chemoresistant epithelial ovarian cancer (EOC) cells to their chemosensitive counterparts and determine their impact on angiogenesis. Methods: Two human EOC cell lines, MDAH-2774 and SKOV-3, and their cisplatin- or taxotere-resistant counterparts were used. Total RNA and protein were subjected to real-time reverse transcriptase–polymerase chain reaction, immunoprecipitation/Western blot and enzyme-linked immunosorbent assay to evaluate the expression of VEGF, VEGF receptors (R1 and R2), and HIF-1α. Angiogenesis was assessed with an in vitro angiogenesis assay. Data were analyzed using independent Student t tests and chi-square. Results: Both taxotere- and cisplatin-resistant MDAH-2774 and SKOV-3 EOC cell lines manifested a significant decrease in VEGF, VEGF receptors, HIF-1α messenger RNA, and protein levels as compared to their chemosensitive counterparts. There was a significant decrease in the number and thickness of polygon blood vessel formation in chemoresistant EOC cells compared to chemosensitive counterparts. Conclusion: Cisplatin- and taxotere-resistant EOC cells are characterized by lower VEGF, VEGF receptors, and HIF-1α, and decreased angiogenesis. These findings may indicate a decrease in drug delivery at the tumor site, hence allowing the persistence of chemoresistant EOC cells.