Over-expression of angiotensin II type 2 receptor gene induces cell death in lung adenocarcinoma cells.
The endogenous angiotensin II (Ang II) type 2 receptor (AT 2) has been shown to mediate apoptosis in cardiovascular tissues. Thus, the aim of this study was to explore the anti-cancer effect of AT 2 over-expression on lung adenocarcinoma cells in vitro using adenoviral (Ad), FuGENE, and nanoparticle vectors. All three gene transfection methods efficiently transfected AT 2 cDNA into lung cancer cells but caused minimal gene transfection in normal lung epithelial cells. Ad-AT 2 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 AT 2 over-expression. Western Blot analysis confirmed the activation of caspase-3. Similarly, poly (lactide-co-glycolic acid) (PLGA) biodegradable nanoparticles encapsulated AT 2 plasmid DNA were shown to be effectively taken up into the lung cancer cell. Nanoparticle-based AT 2 gene transfection markedly increased AT 2 expression and resultant cell death in A549 cells. These results indicate that AT 2 over-expression 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.
Pickel
Lara
L
Department of Anatomy & Physiology, Kansas State University College of Veterinary Medicine, Manhattan, KS 66506, USA.
Matsuzuka
Takaya
T
Department of Anatomy & Physiology, Kansas State University College of Veterinary Medicine, Manhattan, KS 66506, USA.
Doi
Chiyo
C
Department of Anatomy & Physiology, Kansas State University College of Veterinary Medicine, Manhattan, KS 66506, USA.
Ayuzawa
Rie
R
Department of Anatomy & Physiology, Kansas State University College of Veterinary Medicine, Manhattan, KS 66506, USA.
Maurya
Dharmendra Kumar
DK
Department of Anatomy & Physiology, Kansas State University College of Veterinary Medicine, Manhattan, KS 66506, USA.
Xie
Sheng-Xue
SX
Department of Pharmaceutical Chemistry, Kansas University, Lawrence, KS 66045, USA.
Berkland
Cory
C
Department of Pharmaceutical Chemistry, Kansas University, Lawrence, KS 66045, USA.
Tamura
Masaaki
M
Department of Anatomy & Physiology, Kansas State University College of Veterinary Medicine, Manhattan, KS 66506, USAmtamura@vet.k-state.edu.
D000230:Adenocarcinoma / Q000235:genetics / Q000473:pathology* / Q000628:therapy; D000077192:Adenocarcinoma of Lung; D000256:Adenoviridae / Q000235:genetics; D000818:Animals; D017209:Apoptosis; D045744:Cell Line, Tumor; D018014:Gene Transfer Techniques; D015316:Genetic Therapy; D005822:Genetic Vectors; D006801:Humans; D008055:Lipids; D008175:Lung Neoplasms / Q000235:genetics / Q000473:pathology* / Q000628:therapy; D051379:Mice; D053758:Nanoparticles; D044139:Receptor, Angiotensin, Type 2 / Q000235:genetics / Q000378:metabolism*
C411955:FuGene; D008055:Lipids; D044139:Receptor, Angiotensin, Type 2