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

醋酸甲羟孕酮和夫马洁林合成类似物对子宫内膜癌的影响

基本信息

批准号：
06454474
负责人：
TERAKAWA Naoki
金额：
$ 3.97万
依托单位：
Tottori University, Faculty of Medicine
依托单位国家：
日本
项目类别：
Grant-in-Aid for General Scientific Research (B)
财政年份：
1994
资助国家：
日本
起止时间：
1994 至 1995
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-06454474/
关键词：
Endometrial Cancer Nood mouse model Anti-tumor effect Medroxyprogesterone acetate Synthetic analogue of fumagillin Growth inhibition Inhibition of angiogenesis 血管新生阻害剤プロゲスチン併用療法

项目摘要

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

本研究旨在探讨醋酸甲羟孕酮（MPA）和富马青霉素合成类似物（TNP-470）对人子宫内膜腺癌生长的影响。用E_2微球刺激雄性裸鼠皮下接种子宫内膜腺癌细胞ECC-1细胞。接种2周后，当肿瘤大小达到8.0<正负>0.2 mm时，将子宫内膜腺癌动物随机分为4组：单独给药（对照）、MPA （10mg/kg体重）、TNP-470 （30mg/kg体重）、MPA和TNP-470联合给药。每2天给药1次，连续8周。MPA可明显抑制肿瘤的增大，且在治疗2周后抑制作用明显。另一方面，血管生成抑制剂TNP-470对肿瘤大小增加的抑制作用不显著。MPA单用与MPA与TNP-470合用对肿瘤的缩小程度无显著差异。接下来，我们研究了MPA治疗肿瘤减少的机制。经MPA治疗后，肿瘤移植物明显坏死。对肿瘤进行血管计数和血管生成生长因子（bFGF和tgf - α）的免疫组化染色。MPA和TNP-470均未显著降低肿瘤中血管数量和bFGF和tgf - α免疫染色强度。为了解MPA处理是否诱导肿瘤细胞凋亡，缩小肿瘤大小，对移植物进行TUNEL染色。对照组和mpa处理组之间的染色强度无显著差异。最后用PCNA染色法检测肿瘤细胞的增殖能力。结果发现，mpa处理的肿瘤中，pcna阳性细胞的数量明显减少。本研究通过裸鼠模型系统，揭示了MPA对子宫内膜腺癌的抗肿瘤作用机制。然而，在该系统中未发现血管生成抑制剂对腺癌的抗增殖作用。少