| 2-Methoxyestradiol (2-ME), formerly regarded as an inactive metabolite of 17B-estradiol, is now known to be a novel and potent anti-proliferative, pro-apoptotic and anti-angiogenic agent with few adverse effects in clinical trials for the treatment of breast and some animal models of solid tumor. Moreover, the synergistic combination of anti-proliferative and anti-angiogenic properties was potentially encompassed within one molecule. These observations suggested that 2-ME would probably be a superior treatment than utilising a combination of several agents.2-ME is currently being evaluated in PhaseⅡclinical trials for the treatment of solid tumors and is undergoing preclinical evaluation for anti-tumor study. However poor bioavailability and poor dissolubility show that 2-ME is a suboptimal therapeutic agent in its current preparation. In the present study,2-ME was encapsulated in liposome, the antitumor activity of 2-ME liposome (2-methoxyestradiol liposome,2-ME-L) was examined on S180 ascites tumor, H22 Hepatocellular carcinoma and EC9706 transplantable tumor. Discuss the antitumor mechanism of these three carcinoma initially. The differences of antitumor activity between 2-ME-L and 2-ME-S is compared in this research. And the abstract of this article is showed as follows:1. Our purpose in part one is to research the the internal anti-tumor therapy of administrated 2-ME-L was investigated in the S180 ascites mouse model. One hundred and twenty Kunming mice with ascites tumor were distributed into six groups at random:control group,5-fluorouracil group,2-ME-S 22.5 mg·kg-1·d-1 group,2-ME-L 30 mg·kg-1d·-1 group,2-ME-L 22.5 mg·kg-1·d-1 group,2-ME-L 15 mg·kg-1·d-1 group. Treatments were started after 24 h. All the treatments were given 7 times and the interval was 24h. The abdominal circumference of the mice were recorded in all groups every two days. After treatment the survival rate, ascites volume inhibition and cell persistence of mice were evaluated as well as the cell cycle and apoptosis. After HE staining, the pathologica changes of liver were observed by optical microscope. Intraperitoneal administration of 2-methoxyestradiol liposome is effective for the treatment of S180 ascites mice, and could inhibite metastasis of ascites cell in abdominal cavity. The curative effect is dose-dependent, and better than 2-ME solution.2. In part two, the study demonstrated that 2ME is a potent anti-proliferative, pro-apoptotic, anti-angiogenic inhibitor in mice bearing H22 hepatocellular carcinoma. The murine H22 hepatocarcinoma were served as an ectopic solid tumor model. After 24h, the mice were distributed into six groups at random: model group, control group,5-fluorouracil group,2-ME-L 30 mg·kg-1·d-1 group, 2-ME-L 22.5 mg·kg-1·d-1 group,2-ME-L 15 mg·kg-1·d-1 group.. The effects of antitumor therapy were evaluated by testing the growth of tumor, measuring tumor weight or volume, observing the inhibition rate of tumor weight or volume and H&E staining of tissues. The synergistic mechanism of 2-ME therapy was elucidated by detecting the change of expression of pathognostic factors like VEGF, Ki-67, CD34 and so on in tumor microenvironment.2-ME-L significantly suppressed tumor growth. The morphological changes of tumor indicated that tumor in the treatment groups were effectively confined with few surrounding angiogenesis. Tumor cells of the treatment groups groups had abundant necrosis areas with few nucleus in pathological fissile phase. Less immunohistochemical expression of VEGF, Ki-67 and CD34 was found in treatment groups. And the antitumor activity of 2-ME-L was better than 2-ME-S.3. In part three, our purpose in this study is to research the internal anti-tumor therapy of administrated 2-ME-L in EC9706 esophageal cancer model, and to discuss the relative mechanism in the therapy of 2-ME-L. The esophageal cancer EC9706 cells were implanted into the BALB/c mice by subcutaneous injection, which were served as an ectopic solid tumor model. The effects of antitumor therapy were evaluated by testing the growth of tumor, measuring tumor weight or volume, observing the inhibition rate of tumor weight or volume and H&E staining of tissues. The synergistic mechanism of 2-ME therapy was elucidated by detecting the change of expression of pathognostic factors like VEGF, Ki-67, EGF, HIF-1a and so on in tumor microenvironment. In the result,2-ME-L significantly suppressed tumor growth. The morphological changes of tumor indicated that tumor in the treatment groups were effectively confined with few surrounding angiogenesis. Tumor cells of the treatment groups groups had abundant necrosis areas with few nucleus in pathological fissile phase. Less immunohistochemical expression of VEGF, Ki-67, HIF-1a and EGF was found in treatment groups. Intraperitoneal administration of 2-ME-L is effective for the treatment of S180 ascites mice, and could inhibite metastasis of ascites cell in abdominal cavity. The curative effect is dose-dependent.2-ME-L can suppressed the growth of H22 and EC9706 solid tumor and possessed anti-proliferative, pro-apoptotic, anti-angiogenic activity. So 2-ME-L could be of potential use in the treatment of cancer.
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