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- Title
Inhibition of matrix metalloproteinase-2 enhances radiosensitivity by abrogating radiation-induced FoxM1-mediated G2/M arrest in A549 lung cancer cells.
- Authors
Chetty, Chandramu; Bhoopathi, Praveen; Rao, Jasti S.; Lakka, Sajani S.
- Abstract
Matrix metalloproteinase-2 (MMP-2), is known to degrade the collagen IV, plays a role in radiation-induced lung injury. We therefore investigated the antitumor effects of combining MMP-2 inhibition using an adenovirus expressing siRNA against MMP-2 (Ad-MMP-2-Si) with radiation therapy (IR) on A549 lung cancer cells in vitro and in vivo. IR increased MMP-2 mRNA, protein and activity in lung cancer cells. MMP-2 inhibition along with IR enhanced radiosensitivity as determined by clonogenic assay, flow cytometry and TUNEL assay. We show that MMP-2 inhibition prior to irradiation reduced p53 phosphorylation, with a corresponding reduction in the expression of the p53 downstream target gene p21
- Publication
International Journal of Cancer, 2009, Vol 124, Issue 10, p2468
- ISSN
0020-7136
- Publication type
Article
- DOI
10.1002/ijc.24209