We have examined the ability of bryostatin 1 to inhibit the in vitro growth and in vivo development of a panel of four murine tumors of diverse tissue origins. A wide range of antiproliferative responses was observed for the four tumors. At 100 ng/ml the in vitro growth of the Renca renal adenocarcinoma, the B16 melanoma, the M5076 reticulum cell sarcoma, and the L10A B-cell lymphoma were inhibited by 0, 40, 40, and 94% respectively. All three cell lines sensitive to bryostatin in vitro responded to multiple dose, 1 μg/injection/day in vivo i.p., bryostatin therapy. Only the in vitro resistant Renca tumor failed to respond to bryostatin in vivo. The correlation between in vitro and in vivo antitumor efficacy suggests a direct mechanism of antitumor activity for bryostatin. Both local regional therapy (M5076 i.p.) and systemic therapy (B16 lung metastases and L10A s.c. tumors) with bryostatin were successful at prolonging survival time. Multiple i.p. doses of bryostatin at a minimum level of 0.5–1.0 μg/injection were required to observe significant in vivo antitumor effects. The success of in vivo administration of bryostatin in mice bearing 8–10-mm s.c. masses of L10A lymphoma (5–10 × 109) and our further observation that five of a panel of six human B-cell lymphoma cell lines were sensitive to the growth inhibitory effects of bryostatin in vitro suggest that bryostatin may be effective in treating lymphoid malignancies in humans.
This project has been funded at least in part with Federal funds from the Department of Health and Human Services under Contract N01-CO-74102 with Program Resources, Inc./DynCorp. The content of this publication does not necessarily reflect the views or policies of the Department of Health and Human Services, nor does mention of trade names, commercial products, or organizations imply endorsement by the United States Government. By acceptance of this article, the publisher or recipient acknowledges the right of the United States Government to retain a nonexclusive, royalty-free license in and to any copyright covering the article.