Additive cytotoxicity of adriamycin and a naturally occurring growth inhibitor extracted from bovine aorta

A factor of nominal molecular weight 6K–10K Daltons, isolated from bovine aorta, has previously been shown to inhibit neovascularization and tumor growth in vivo and the growth of some tumor cells as well as endothelial cells in culture. This factor, termed A-10, was tested alone and in combination with Adriamycin against TA3Ha mammary adenocarcinoma cells in tissue culture. It was found to have cytotoxicity additive to that of Adriamycin in inhibiting the growth of these cells. In vitro and animal studies show that the sequence of Adriamycin A-10 is superior to either agent alone in delaying the appearance of palpable tumors after subcutaneous injection of 10⁵ pre-treated tumor cells in the tail of strain A mice. While the growth rate of the primary tumor was not affected by such treatment, survival was prolonged to a greater degree by the this sequence than by either of these agents used alone. A-10 treatment reduced the number of metastases to the adrenal gland but not to lung, liver, or lymph nodes. It did, however, reduce the size of metastases to para-aortic lymph nodes.