Stable RNA interference-mediated suppression of cyclophilin A diminishes non-small-cell lung tumor growth in vivo.

Published

Journal Article

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.

Full Text

Duke Authors

Cited Authors

  • Howard, BA; Furumai, R; Campa, MJ; Rabbani, ZN; Vujaskovic, Z; Wang, X-F; Patz, EF

Published Date

  • October 2005

Published In

Volume / Issue

  • 65 / 19

Start / End Page

  • 8853 - 8860

PubMed ID

  • 16204056

Pubmed Central ID

  • 16204056

Electronic International Standard Serial Number (EISSN)

  • 1538-7445

International Standard Serial Number (ISSN)

  • 0008-5472

Digital Object Identifier (DOI)

  • 10.1158/0008-5472.can-05-1219

Language

  • eng