Abstract

Angiogenesis is critical for progressive tumor growth and metastasis. Tumors progress from a prevascular stage to a vascular stage and the vascularized stage permits metastasis. Regulatory mechanisms of the angiogenic process are known to be directly and indirectly related to various angiogenic factors. Recently angiogenesis became an appealing therapeutic modality for the treatment of human malignancies, especially breast cancer. However such an approach has remained little more than good theory. And the clinical field of antiangiogenic therapy stays in its infancy. To evaluate a possibility of antiangiogenic treatment on breast cancer, the author performed an experiment to investigate antiangiogenic activity of pentosan polysulfate(PPS) and medroxyprogesterone acetate(MPA) on 9,10-dimethyl-1,2-benianthracene(DMBA) induced mammary tumors of female Sprague-Dawley rats. The angiogenic and antiangiogenic activities were observed by response rate of the tumor volume, histologic grading and changes, and microvessel densities of the tumors on immunoperoxidase staining for factor VIII-related antigen. The results are followings: 1) Induction rate of mammary tumor after DMBA treatment was 80.1% and about 95% of these tumors were adenocarcinoma. 2) Response rate of mammary carcinoma to MPA and PPS treatment was 45.1% and 40.0% , respectively, and is statistically significant compared with the test control group(p<0. 05). 3) Necrosis was more marked and frequent in tumors of the PPS group than test control group and the histologic grade was lower in the PPS and MPA group than the test control. 4) Microvessel densities of the tumors were significantly lower in the PPS and MPA groups(p<0.05) than the test contral, but there was no significant difference between these two groups(p>0.05). 5) The difference of microvessel density according to response rate tended to be lower in partial response group than in progressive disease group of the test control and PPS groups. In summary, it is concluded that PPS and MPA have antitumor effect on chemically induced rat mammery carcinoma and the antitumor effect of PPS and MPA is related to antiangiogenesis.

• Keywords: Breast cancer, 9,10-dimethyl-l,2-benzanthracene(DMBA), Pentosan polysulfate, Medroxyprogesterone acetate, Angiogenesis