anti-matrix metalloproteinase-9 dnazyme decreases tumor growth in the mmtv-pymt mouse model of breast canceranti-matrix metalloproteinase-9 dnazyme减少肿瘤增长mmtv-pymt乳腺癌的老鼠模型.pdfVIP

Hallett et al. Breast Cancer Research 2013, 15:R12 /content/15/1/R12 RESEARCH ARTICLE Open Access Anti-matrix metalloproteinase-9 DNAzyme decreases tumor growth in the MMTV-PyMT mouse model of breast cancer 1 1 1 2 2 Miranda A Hallett , Bin Teng , Hisashi Hasegawa , Luciana P Schwab , Tiffany N Seagroves and Tayebeh Pourmotabbed 1* Abstract Introduction: Despite continued improvements in diagnosis, surgical techniques, and chemotherapy, breast cancer patients are still overcome by cancer metastasis. Tumor cell proliferation, invasion and metastasis are mediated, at least in part, through degradation of basement membrane by neutral matrix metalloproteinases (MMP) produced by tumor and stromal cells. Evidence suggests that MMP-9 plays a significant role in breast tumor cell invasion and metastasis. DNAzymes or catalytic oligonucleotides are new classes of gene targeting molecules that bind and cleave a specific mRNA, resulting in decreased protein expression. Methods: The application of anti-MMP-9 DNAzyme (AM9D) for the treatment of primary and metastatic breast cancer was evaluated in vitro and in vivo using MDA-MB-231 cells and the MMTV-PyMT transgenic breast cancer mouse model. Spontaneously developed mammary tumors in MMTV-PyMT transgenic mice were treated intratumorally with naked AM9D, once a week for 4 weeks. The stability of DNAzyme was determined in vitro and in vivo using fluorescently labeled DNAzyme. Results: AM9D specifically inhibited expression of MMP-9 in MDA-MB-231 cells resulting in reduced invasive property of these cells by 43%. Weekly intratumoral treatment of spontaneously developed mammary tumors in MMTV-PyMT transgenic mice was sufficient to significantly reduce the ra