recombinant lysyl oxidase propeptide protein inhibits growth and promotes apoptosis of pre-existing murine breast cancer xenografts赖氨酰化氧前肽重组蛋白抑制增长和促进细胞凋亡的预先存在的小鼠乳腺癌异种移植.pdfVIP

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recombinant lysyl oxidase propeptide protein inhibits growth and promotes apoptosis of pre-existing murine breast cancer xenografts赖氨酰化氧前肽重组蛋白抑制增长和促进细胞凋亡的预先存在的小鼠乳腺癌异种移植.pdf

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recombinant lysyl oxidase propeptide protein inhibits growth and promotes apoptosis of pre-existing murine breast cancer xenografts赖氨酰化氧前肽重组蛋白抑制增长和促进细胞凋亡的预先存在的小鼠乳腺癌异种移植

Recombinant Lysyl Oxidase Propeptide Protein Inhibits Growth and Promotes Apoptosis of Pre-Existing Murine Breast Cancer Xenografts 1 2 1 1 2 Manish V. Bais , Matthew A. Nugent , Danielle N. Stephens , S. Selva Sume , Kathrin H. Kirsch , Gail E. Sonenshein3, Philip C. Trackman1,2* 1 Division of Oral Biology, Boston University Henry M. Goldman School of Dental Medicine, Boston, Massachusetts, United States of America, 2 Department of Biochemistry, Boston University School of Medicine, Boston, Massachusetts, United States of America, 3 Department of Biochemistry, Tufts University School of Medicine, Boston, Massachusetts, United States of America Abstract Lysyl oxidase propeptide (LOX-PP) ectopic overexpression inhibits the growth of cancer xenografts. Here the ability and mode of action of purified recombinant LOX-PP (rLOX-PP) protein to inhibit the growth of pre-existing xenografts was determined. Experimental approaches employed were direct intratumoral injection (i.t.) of rLOX-PP protein into murine breast cancer NF639 xenografts, and application of a slow release formulation of rLOX-PP implanted adjacent to tumors in NCR nu/nu mice (n = 10). Tumors were monitored for growth, and after sacrifice were subjected to immunohistochemical and Western blot analyses for several markers of proliferation, apoptosis, and for rLOX-PP itself. Direct i.t. injection of rLOX- PP significantly reduced tumor volume on days 20, 22 and 25 and tumor weight at harvest on day 25 by 30% compared to control. Implantation of beads preloaded with 35 micrograms rLOX-PP (n = 10) in vivo reduced tumor volume and weight at sacrifice when compared to empty beads (p,0.05). A 30% reduction of tumor volume on days 22 and 25 (p,0.05) and final tu