Direct action by doxycycline against canine osteosarcoma cell proliferation and collagenase (MMP-1) activity in vitro

Background: Matrix metalloproteinases (MMPs) produced by tumor cells disrupt the integrity of the extracellular matric (EM). Inhibiting MMPs activity could significantly reduce tumor invasion and metastasis. Materials and Methods: Canine osteosarcoma (OSA) cells were exposed to doxycycline in vitro to determine whether this chemically modified tetracycline had antiproliferative and anticollagenolytic activity. Results: Doxycycline significantly reduced cell proliferation in a dose dependent manner. Doxycycline at the doses of 5 and 10 mu g/ml suppressed cell number 50% and 72%, respectively. Furthermore, doxycycline significantly reduced collagenase activity at the doses of 10 and 20 mu g/ml by 35% and 50%, respectively. OSA cells did not produce any endogenous collagenase in the culture medium. Conclusions: This study has shown that doxycycline at doses greater than 5 mu g/ml in vitro significantly decreases cell proliferation and collagenase (MMP-1) activity. Prospective studies should be conducted to determine if doxycycline, a chemically modified tetracycline with low systemic toxicity, has specific anti-collagenase activity in vivo. Our studies indicate that canine osteosarcoma represents a suitable model for additional in vitro and in vivo studies.