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Zhonghua Fu Chan Ke Za Zhi ; 40(9): 631-5, 2005 Sep.
Article in Chinese | MEDLINE | ID: mdl-16202322

ABSTRACT

OBJECTIVE: To evaluate the effects of 2-methoxyestradiol (2-ME(2)) on human cervical cancer HeLaS3 cells and cervical cancer xenografts. METHODS: Cell proliferation assay and cell cycle analysis were used to measure HeLaS3 cell growth and cell cycle progression after 2-ME(2) treatment. Fluorescent microscopy to observe the cell morphology and DNA electrophoresis to measure apoptosis. In addition, the effect of 2-ME(2) on the expression of inducible nitric oxide synthase (iNOS) was measured by Western blot. Moreover, human cervical cancer model was set up using HeLaS3 cells and 2-ME(2) (75 mg/kg) was orally given for 14 d. Tumor volume was determined and apoptosis was detected by in situ cell death. RESULTS: Newly-formed cell amount in treated group was 81% of that in control group after 1 micromol/L 2-ME(2) treatment for 48 h (P < 0.05), and was 19% of that in control group after 2-ME(2) treatment for 96 h (P < 0.01). G(2)/M phase cells were increased to 55% from 16% of the control (P < 0.01), and apoptotic cells were increased to 16% from 4% of the control, after 5 micromol/L 2-ME(2) treatment for 20 h. Nuclear condensation and abnormal metaphase cells were found by fluorescent microscopy. Typical DNA ladder was found by DNA electrophoresis. And the expression of iNOS was increased by 2-ME(2) in a time- and concentration-dependent manner, in parallel with apoptosis. Moreover, apoptosis was prevented by the iNOS inhibitor 1400W. In vivo, tumor volume was reduced 34% while compared with the control group. In situ cell death detection found more apoptotic and necrotic cells in 2-ME(2)-treated group. CONCLUSIONS: 2-ME(2) inhibits human cervical cancer HeLaS3 cells and tumor growth in cervical cancer xenografts. Thus 2-ME(2) has the therapeutic potential for cervical carcinoma.


Subject(s)
Estradiol/analogs & derivatives , Uterine Cervical Neoplasms/prevention & control , Xenograft Model Antitumor Assays , 2-Methoxyestradiol , Amidines/pharmacology , Animals , Apoptosis/drug effects , Benzylamines/pharmacology , Cell Cycle/drug effects , Cell Nucleus/drug effects , Cell Nucleus/metabolism , Dose-Response Relationship, Drug , Estradiol/pharmacology , Estradiol/therapeutic use , Female , HeLa Cells , Humans , Mice , Mice, SCID , Microscopy, Fluorescence , Nitric Oxide Synthase/antagonists & inhibitors , Nitric Oxide Synthase/biosynthesis , Tumor Burden , Uterine Cervical Neoplasms/metabolism , Uterine Cervical Neoplasms/pathology
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