Overexpression of angiotensin II type 2 receptor gene induces cell death in lung adenocarcinoma cells

Abstract

The endogenous angiotensin II (ang II) type 2 receptor (AT2) has been shown to mediate apoptosis in cardiovascular tissues. Thus, the aim of this study was to explore the anticancer effect of AT2 overexpression on lung adenocarcinoma cells in vitro using adenoviral (ad), FuGeNe, and nanoparticle vectors. All three gene transfection methods efficiently transfected AT2 cDNa into lung cancer cells but caused minimal gene transfection in normal lung epithelial cells. Ad-AT2 significantly attenuated multiple human lung cancer cell growth (A549 and H358) as compared to the control viral vector, Ad-LacZ, when cell viability was examined by direct cell count. Examination of annexin V by flow cytometry revealed the activation of the apoptotic pathway via AT2 overexpression. Western blot analysis confirmed the activation of caspase-3. Similarly, poly (lactide-co-glycolic acid) (PLGA) biodegradable nanoparticles encapsulated AT2 plasmid DNA were shown to be effectively taken up into the lung cancer cell. Nanoparticle-based AT2 gene transfection markedly increased AT2 expression and resultant cell death in A549 cells. These results indicate that AT2 overexpression effectively attenuates growth of lung adenocarcinoma cells through intrinsic apoptosis. Our results also suggest that PLGA nanoparticles can be used as an efficient gene delivery vector for lung adenocarcinoma targeted therapy. © 2010 Landes Bioscience.