title: Complete estrogen receptor blocker ICI182,780 promotes the proliferation of vascular smooth muscle cells.
abstract: 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, immunochemical 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(-5) 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.
authors.affiliation: Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education and Chinese Ministry of Health, Shandong University, Jinan, China.
authors.forename: Hong
authors.initials: H
authors.lastname: He
authors.forename: Falin
authors.initials: F
authors.lastname: Yang
authors.forename: Xin
authors.initials: X
authors.lastname: Wang
authors.forename: Xianwei
authors.initials: X
authors.lastname: Zeng
authors.forename: Qin
authors.initials: Q
authors.lastname: Hu
authors.forename: Jinghuan
authors.initials: J
authors.lastname: Huang
authors.forename: Jinbo
authors.initials: J
authors.lastname: Feng
mesh_terms: D000818:Animals; D001943:Breast Neoplasms / Q000188:drug therapy; D002455:Cell Division / Q000187:drug effects*; D002460:Cell Line / Q000187:drug effects; D019938:Cyclin D1 / Q000187:drug effects / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004958:Estradiol / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000494:pharmacology; D004965:Estrogen Antagonists / Q000009:adverse effects* / Q000494:pharmacology; D005260:Female; D000077267:Fulvestrant; D009131:Muscle, Smooth, Vascular / Q000166:cytology*; D032389:Myocytes, Smooth Muscle / Q000187:drug effects* / Q000378:metabolism; D018809:Proliferating Cell Nuclear Antigen / Q000187:drug effects* / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D011960:Receptors, Estrogen / Q000037:antagonists & inhibitors*; D016196:S Phase / Q000187:drug effects
chemical_list: D004965:Estrogen Antagonists; D018809:Proliferating Cell Nuclear Antigen; D011960:Receptors, Estrogen; D019938:Cyclin D1; D000077267:Fulvestrant; D004958:Estradiol