Complete estrogen receptor blocker ICI182,780 promotes the proliferation of vascular smooth muscle cells

ICI182,780 is used in adjuvant therapies of breast cancer. As a complete estrogen receptor (ER) blocker, ICI182,780 may antagonize the effects of estrogen on the cardiovascular system. Estrogen inhibits the proliferation of vascular smooth muscle cells (VSMCs), which is one of the mechanisms that es...

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Veröffentlicht in:Acta biochimica et biophysica Sinica 2011-02, Vol.43 (2), p.118-123
Hauptverfasser: He, Hong, Yang, Falin, Wang, Xin, Zeng, Xianwei, Hu, Qin, Huang, Jinghuan, Feng, Jinbo
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container_start_page 118
container_title Acta biochimica et biophysica Sinica
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creator He, Hong
Yang, Falin
Wang, Xin
Zeng, Xianwei
Hu, Qin
Huang, Jinghuan
Feng, Jinbo
description ICI182,780 is used in adjuvant therapies of breast cancer. As a complete estrogen receptor (ER) blocker, ICI182,780 may antagonize the effects of estrogen on the cardiovascular system. Estrogen inhibits the proliferation of vascular smooth muscle cells (VSMCs), which is one of the mechanisms that estrogen can exert cardioprotective effects. In the present study, to assess the effects of ICI182,780 on the proliferation of VSMCs, we cultured VSMCs isolated from rat aorta with or without the ER antagonist ICI182,780. The results of 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay, bromodeoxyuridine incorporation assay, viable cell count, immunochemicai staining for proliferating cell nuclear antigen (PCNA), and S-phase ratio determined by flow cytometry revealed a remarkable proliferation of VSMCs after ICI182,780 treatment. ICI182,780 significantly enhanced cell growth in a dose-dependent manner (10-8-10-s M). Furthermore, the number of PCNA-positive cells and the S-phase progression of VSMCs increased after treatment with ICI182,780. Reverse transcriptase-polymerase chain reaction (RT-PCR) and western blot analysis showed that the mRNA and protein level of cyclin D1 in VSMCs increased under the treatment of ICI182,780. These data suggested that ICI182,780 can promote the growth of VSMCs, which might produce some adverse effects on the cardiovascular system.
doi_str_mv 10.1093/abbs/gmq119
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As a complete estrogen receptor (ER) blocker, ICI182,780 may antagonize the effects of estrogen on the cardiovascular system. Estrogen inhibits the proliferation of vascular smooth muscle cells (VSMCs), which is one of the mechanisms that estrogen can exert cardioprotective effects. In the present study, to assess the effects of ICI182,780 on the proliferation of VSMCs, we cultured VSMCs isolated from rat aorta with or without the ER antagonist ICI182,780. The results of 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay, bromodeoxyuridine incorporation assay, viable cell count, immunochemicai staining for proliferating cell nuclear antigen (PCNA), and S-phase ratio determined by flow cytometry revealed a remarkable proliferation of VSMCs after ICI182,780 treatment. ICI182,780 significantly enhanced cell growth in a dose-dependent manner (10-8-10-s M). Furthermore, the number of PCNA-positive cells and the S-phase progression of VSMCs increased after treatment with ICI182,780. Reverse transcriptase-polymerase chain reaction (RT-PCR) and western blot analysis showed that the mRNA and protein level of cyclin D1 in VSMCs increased under the treatment of ICI182,780. 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As a complete estrogen receptor (ER) blocker, ICI182,780 may antagonize the effects of estrogen on the cardiovascular system. Estrogen inhibits the proliferation of vascular smooth muscle cells (VSMCs), which is one of the mechanisms that estrogen can exert cardioprotective effects. In the present study, to assess the effects of ICI182,780 on the proliferation of VSMCs, we cultured VSMCs isolated from rat aorta with or without the ER antagonist ICI182,780. The results of 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay, bromodeoxyuridine incorporation assay, viable cell count, immunochemicai staining for proliferating cell nuclear antigen (PCNA), and S-phase ratio determined by flow cytometry revealed a remarkable proliferation of VSMCs after ICI182,780 treatment. ICI182,780 significantly enhanced cell growth in a dose-dependent manner (10-8-10-s M). Furthermore, the number of PCNA-positive cells and the S-phase progression of VSMCs increased after treatment with ICI182,780. Reverse transcriptase-polymerase chain reaction (RT-PCR) and western blot analysis showed that the mRNA and protein level of cyclin D1 in VSMCs increased under the treatment of ICI182,780. These data suggested that ICI182,780 can promote the growth of VSMCs, which might produce some adverse effects on the cardiovascular system.</description><subject>Animals</subject><subject>Breast Neoplasms - drug therapy</subject><subject>Cell Division - drug effects</subject><subject>Cell Line - drug effects</subject><subject>Cyclin D1 - drug effects</subject><subject>Cyclin D1 - metabolism</subject><subject>Dose-Response Relationship, Drug</subject><subject>Estradiol - adverse effects</subject><subject>Estradiol - analogs &amp; derivatives</subject><subject>Estradiol - pharmacology</subject><subject>Estrogen Antagonists - adverse effects</subject><subject>Estrogen Antagonists - pharmacology</subject><subject>Female</subject><subject>Muscle, Smooth, Vascular - cytology</subject><subject>Myocytes, Smooth Muscle - drug effects</subject><subject>Myocytes, Smooth Muscle - metabolism</subject><subject>Proliferating Cell Nuclear Antigen - drug effects</subject><subject>Proliferating Cell Nuclear Antigen - metabolism</subject><subject>Rats</subject><subject>Rats, Wistar</subject><subject>Receptors, Estrogen - antagonists &amp; 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Furthermore, the number of PCNA-positive cells and the S-phase progression of VSMCs increased after treatment with ICI182,780. Reverse transcriptase-polymerase chain reaction (RT-PCR) and western blot analysis showed that the mRNA and protein level of cyclin D1 in VSMCs increased under the treatment of ICI182,780. These data suggested that ICI182,780 can promote the growth of VSMCs, which might produce some adverse effects on the cardiovascular system.</abstract><cop>China</cop><pmid>21193431</pmid><doi>10.1093/abbs/gmq119</doi><tpages>6</tpages></addata></record>
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subjects Animals
Breast Neoplasms - drug therapy
Cell Division - drug effects
Cell Line - drug effects
Cyclin D1 - drug effects
Cyclin D1 - metabolism
Dose-Response Relationship, Drug
Estradiol - adverse effects
Estradiol - analogs & derivatives
Estradiol - pharmacology
Estrogen Antagonists - adverse effects
Estrogen Antagonists - pharmacology
Female
Muscle, Smooth, Vascular - cytology
Myocytes, Smooth Muscle - drug effects
Myocytes, Smooth Muscle - metabolism
Proliferating Cell Nuclear Antigen - drug effects
Proliferating Cell Nuclear Antigen - metabolism
Rats
Rats, Wistar
Receptors, Estrogen - antagonists & inhibitors
S Phase - drug effects
受体拮抗剂
增殖细胞核抗原
心血管系统
细胞增殖
血管平滑肌细胞
辅助治疗
逆转录聚合酶链反应
雌激素受体
title Complete estrogen receptor blocker ICI182,780 promotes the proliferation of vascular smooth muscle cells
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