title: Doxycycline decreases tumor burden in a bone metastasis model of human breast cancer.
abstract: Bone is one of the most frequent sites for metastasis in breast cancer patients,often resulting in significant clinical morbidity and mortality. Increased matrix metalloproteinase (MMP) activity of tumor cells correlates with a higher invasive and metastatic potential. Members of the tetracycline family of antibiotics, including doxycycline, have potential treatment value for bone metastasis; they inhibit cancer cell proliferation, and they are also potent MMP inhibitors and are highly osteotropic. Doxycycline treatment in an experimental bone metastasis mouse model of human breast cancer MDA-MB-231 cells resulted in a 70% reduction in total tumor burden when compared with placebo control animals. In tumor-bearing animals, the amount of doxycycline incorporated into the radius/ulna as assessed by ELISA was lower than in non-tumor-bearing animals. In doxycycline-treated mice, bone formation was significantly enhanced as determined by increased numbers of osteoblasts, osteoid surface, and volume, whereas a decrease in bone resorption was also observed. Doxycycline treatment may be beneficial for breast cancer patients with or at risk for osteolytic bone metastasis; it greatly reduces tumor burden and could also compensate for the increased bone resorption associated with the disease.
authors.affiliation: Hamilton Regional Cancer Centre and McMaster University, Hamilton, Ontario, L8V 5C2 Canada.
authors.forename: Wilhelmina C M
authors.initials: WC
authors.lastname: Duivenvoorden
authors.forename: Snezana Vukmirović
authors.initials: SV
authors.lastname: Popović
authors.forename: Sárka
authors.initials: S
authors.lastname: Lhoták
authors.forename: Eric
authors.initials: E
authors.lastname: Seidlitz
authors.forename: Holger W
authors.initials: HW
authors.lastname: Hirte
authors.forename: Richard G
authors.initials: RG
authors.lastname: Tozer
authors.forename: Gurmit
authors.initials: G
authors.lastname: Singh
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy* / Q000556:secondary*; D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D001859:Bone Neoplasms / Q000188:drug therapy* / Q000556:secondary*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000473:pathology*; D004318:Doxycycline / Q000494:pharmacology*; D005260:Female; D006801:Humans; D007269:Injections, Intra-Arterial; D051379:Mice; D008807:Mice, Inbred BALB C; D014407:Tumor Cells, Cultured; D023041:Xenograft Model Antitumor Assays
chemical_list: D000900:Anti-Bacterial Agents; D004318:Doxycycline