Effect of antiangiogenic therapy on slowly growing, poorly vascularized tumors in mice

Background: Angiogenesis is essential for tumor growth and progression. The refore, inhibition of angiogenesis is being studied as a new anticancer the rapy. Because cytotoxic chemotherapy is more effective on rapidly growing t umors than on slowly growing tumors, it has been assumed that antiangiogeni c therapy will, also be effective only on rapidly growing, highly vasculari zed tumors. We compared the effects of two angiogenesis inhibitors, TNP-470 and angiostatin, on slowly growing, poorly vascularized and rapidly growin g, highly vascularized human tumors in mice. Methods: Slowly growing (RT-4) and rapidly growing (MGH-U1) human bladder carcinoma cell lines were grown in severe combined immunodeficiency mice. Established tumors were treated with one of the two angiogenesis inhibitors. Tumor volumes, vascularity, an d proliferation indices were determined. The in vitro effects of TNP-470 an d of angiostatin on the proliferation of RT-4 and MGH-U1 cells were also in vestigated. All statistical tests were two-sided. Results: RT-4 and MGH-U1 tumor growth was statistically significantly inhibited by both angiogenesis inhibitors (P<.001). Both inhibitors decreased the blood vessel density in both tumor types but did not alter the in vivo proliferation indices of th e tumors, TNP-470, but not angiostatin, marginally decreased the in vitro p roliferation of MGH-U1 cells. Conclusion: Slowly growing, poorly vasculariz ed tumors in animal models respond as well as rapidly growing, highly vascu larized tumors to therapy with the angiogenesis inhibitors TNP-470 and angi ostatin.