Abstract 1148: Ang-(1-7) decreases HIF-1α and migration of oral squamous cell carcinoma

Abstract

Abstract induced by cobaltous chloride and the underlying mechanism. Methods and Results We first confirmed that Ang-(1-7) decreases HIF-1α signaling in a newly developed hydroxypropyl-β-cyclodextrin (HPBCD)-based Ang-(1-7) nano-formulation in a novel transgenic rat model of inducible insulin resistance and DM2. The chronic administration of this compound prevented the marked elevation of HIF-1α in diabetic rat kidney. Next, mouse embryonic fibroblasts (MEFs) and SCC-9 cells were incubated in a well humidified incubator with 5% CO2 and 95% air at 37 °C (normoxic condictions). For hypoxic cultures, cells were incubated 150 μM CoCl2 for 24 hours and maintained in a 5% CO2 atmosphere at 37°C. Then, we divided cells into 4 groups including control, CoCl2, Ang-(1-7) and CoCl2 + Ang-(1-7). HIF-1α protein expression and AKT phosphorylation were decreased in hypoxic cells after treatment with Ang-(1-7). Besides, Ang-(1-7) decreased SCC-9 cell migration in hypoxic condition. Conclusions In conclusion, our current findings suggest that Ang-(1-7) attenuates HIF-1 α protein stabilization via AKT and Mas receptor-dependent mechanism. In addition, we found that the Ang-(1-7)/Mas receptor inhibit oral cancer cell migration. Note: This abstract was not presented at the meeting. Citation Format: Andre Luiz Sena Guimaraes, Carlos Alberto de Carvalho Fraga, Lucyana Conceição Farias, Talita Antunes Guimarães, Alfredo Maurício Batista De Paula, Amanda Mota, Lais Santiago, Ricardo Santiago Gomez, Sergio Henrique Sousa Santos, Robson Augusto Souza dos Santos, Michael Bader. Ang-(1-7) decreases HIF-1α and migration of oral squamous cell carcinoma. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 1148. doi:10.1158/1538-7445.AM2015-1148