Stable RNA interference-mediated suppression of cyclophilin A diminishes non-small-cell lung tumor growth in vivo.
Cyclophilin A (CypA) was recently reported to be overexpressed in non-small-cell lung cancer, and represents a potentially novel therapeutic target. To determine the role of CypA in oncogenesis, stable RNA interference (RNAi)-mediated knockdown of CypA was established in two non-small-cell lung cancer cell lines (ADLC-5M2 and LC-103H), and these cells were grown as xenografts in severe combined immunodeficient mice. Tumor cell proliferation, apoptosis, and angiogenesis were measured by Ki67, terminal deoxyribonucleotidyl transferase-mediated dUTP nick-end labeling, and CD31 immunohistochemistry, respectively. Tumor glucose metabolism was assessed by fluorodeoxyglucose positron emission tomography imaging. Knockdown of CypA correlated in vivo with slower growth, less fluorodeoxyglucose uptake, decreased proliferation, and a greater degree of apoptosis in the tumors. These results establish the relevance of CypA to tumor growth in vivo, specifically to proliferation and apoptosis. Elucidation of the precise role of CypA in these pathways may lead to new targeted therapies for lung cancer.
Howard
Brandon A
BA
Department of Radiology, Duke University Medical Center, Durham, North Carolina 27710, USA.
Furumai
Ryohei
R
Campa
Michael J
MJ
Rabbani
Zahid N
ZN
Vujaskovic
Zeljko
Z
Wang
Xiao-Fan
XF
Patz
Edward F
EF
D000818:Animals; D017209:Apoptosis / Q000502:physiology; D002289:Carcinoma, Non-Small-Cell Lung / Q000098:blood supply / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D048708:Cell Growth Processes / Q000502:physiology; D045744:Cell Line, Tumor; D021984:Cyclophilin A / Q000037:antagonists & inhibitors* / Q000096:biosynthesis / Q000235:genetics; D019788:Fluorodeoxyglucose F18 / Q000493:pharmacokinetics; D008175:Lung Neoplasms / Q000098:blood supply / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D051379:Mice; D008819:Mice, Nude; D009389:Neovascularization, Pathologic / Q000378:metabolism; D034622:RNA Interference; D014162:Transfection
D019788:Fluorodeoxyglucose F18; D021984:Cyclophilin A