Fig. 4
The indirect anti-angiogenesis effect of Doxycycline via MMPs inhibition. MMPs increase the secretion of proangiogenic factors like VEGF, bFGF and TGF promoting the formation of new network of blood vessels. Adequate blood supply helps osteosarcoma cells to survive, proliferate and penetrate blood vessels to give metastases in distant organs, mainly in lungs. Doxycycline acts as a cytotoxic agent by inhibiting MMPs and depriving tumor cells from nutritional necessities [35]