Effects of medroxyprogesterone acetate and synthetic analogue of fumagillin on endometrial cancer

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This study was undertaken to investigate the effects of medroxyprogesterone acetate (MPA) and synthetic analogue of fumagillin (TNP-470) on the growth of human endometrial adenocarcinoma. Endometrial adenocarcinoma cells, ECC-1 cells, were inoculated subcutaneously in male nude mice stimulated by sc implantation of E_2 pellet. When the tumor size reached to 8.0<plus-minus>0.2 mm at two weeks after inoculation, the animals with endometrial adenocarcinoma were randomly divided into four groups : mice treated with vehicle alone (control) , MPA (10mg/kg body weight) , TNP-470 (30mg/kg body weight) , or MPA and TNP-470 combination. Vehicle or the compounds were injected sc every two days for 8 weeks. Administration of MPA significantly inhibited the increase in tumor size, and the inhibition became evident 2 weeks after MPA treatment. On the other hand, the suppression of the increase in tumor size by TNP-470, an angiogenic inhibitor, was not significant. There was no difference in the degr … More ee of tumor reduction between the treatments of MPA alone and MPA and TNP-470 combination.We next examined the mechanism of tumor reduction by MPA treatment. After MPA treatment necrosis was evident in the tumor grafts. Vessel counts and immunohistochemical stainings for angiogenic growth factors, bFGF and TGF-alpha, in tumors were carried out. Neither MPA nor TNP-470 significantly reduced the number of vessels and the intensity of immunostainings for bFGF and TGF-alpha in tumors. In order to know whether MPA treatment induced apoptosis of tumor cells and reduced the tumor size, TUNEL stainings were performed in tumor grafts. There was no significant difference in the intensity of staining between the control and MPA-treated groups. Finally, the proliferative ability of tumor cells was examined by the method of PCNA staining. It was found that the number of PCNA-positive cells was remarkably decreased in MPA-treated tumors.In the present study with nude mouse model system, the mechanism of antitumor effect of MPA in endometrial adenocarcinoma was shown. However, antiproliferative effect of an angiogenic inhibitor on adenocarcinoma could not be found in this system. Less