雌激素药理浓度对3AO人卵巢癌细胞生长的影响

LI Zong-Bin, CHEN Yu-Xia, ZHAO Jie-Ying, LU Jian
{"title":"雌激素药理浓度对3AO人卵巢癌细胞生长的影响","authors":"LI Zong-Bin,&nbsp;CHEN Yu-Xia,&nbsp;ZHAO Jie-Ying,&nbsp;LU Jian","doi":"10.1016/S0379-4172(06)60111-X","DOIUrl":null,"url":null,"abstract":"<div><p>During the past two decades, the knowledge of the molecular mechanism by which estrogens exert various functions in different tissues and organs has evolved rapidly. Recent reports demonstrated that estrogen could decrease the cell growth in several types of cancer cells, including ovarian cancer cells. Though experiments explored the possible mechanism of the inhibitory effect, the exact mechanism is responsible for the effect, which remains unclear. The ovary is the main source of the estrogen, estrogen receptor is expressed in several ovarian cell types, including ovarian surface epithelium, the tissue of origin of approximately 90% of the ovarian cancers. It was of great interest to analyze the effects of 17β-estradiol (E2) on apoptosis of ovarian cancer cells, and the identification of E2-regulated specific genes involved in epithelial proliferation apoptosis, thus may be a clue for understanding the progression of ovarian cancer and for the design of new target therapies. To elucidate the mechanism involved, effects of pharmacological concentrations of estrogen were studied in human ovarian cancer cell line 3AO cells. Inhibition of cellular growth of 3AO cells was seen with E2 at concentrations higher than 0.1 μmol/L. The estrogen receptor inhibitor ICI 182780 cannot block the inhibitory effect of E2. It was surprising to find that ICI 182780 itself can inhibit the growth of 3AO cells, and had a collaborative effect with E2. The decreased cell growth induced by E2 was shown to be apoptosis as analyzed by flow cytometry. ERβ was detected in the 3AO ovarian cancer cell line but not ERα. The expression of ERβ was weak, which may partially explain why high but not low dose of E2 needed to induce the apoptosis of 3AO cells. We also observed that membrane impermeable E2, E2-BSA have lost growth inhibitory on 3AO cells, which excluded the membrane effect of E2 as previously reported by many investigators. The p38 kinase inhibitor, SB203580 were partially protected 3AO cells against growth inhibition by E2, while inhibitor of JNK, SP600125 enhanced cell death induced by E2. These results showed that MAPK is implicated in cellular processes involving apoptosis.</p></div>","PeriodicalId":100017,"journal":{"name":"Acta Genetica Sinica","volume":null,"pages":null},"PeriodicalIF":0.0000,"publicationDate":"2006-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/S0379-4172(06)60111-X","citationCount":"5","resultStr":"{\"title\":\"Effects of Pharmacological Concentrations of Estrogens on Growth of 3AO Human Ovarian Cancer Cells\",\"authors\":\"LI Zong-Bin,&nbsp;CHEN Yu-Xia,&nbsp;ZHAO Jie-Ying,&nbsp;LU Jian\",\"doi\":\"10.1016/S0379-4172(06)60111-X\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><p>During the past two decades, the knowledge of the molecular mechanism by which estrogens exert various functions in different tissues and organs has evolved rapidly. Recent reports demonstrated that estrogen could decrease the cell growth in several types of cancer cells, including ovarian cancer cells. Though experiments explored the possible mechanism of the inhibitory effect, the exact mechanism is responsible for the effect, which remains unclear. The ovary is the main source of the estrogen, estrogen receptor is expressed in several ovarian cell types, including ovarian surface epithelium, the tissue of origin of approximately 90% of the ovarian cancers. It was of great interest to analyze the effects of 17β-estradiol (E2) on apoptosis of ovarian cancer cells, and the identification of E2-regulated specific genes involved in epithelial proliferation apoptosis, thus may be a clue for understanding the progression of ovarian cancer and for the design of new target therapies. To elucidate the mechanism involved, effects of pharmacological concentrations of estrogen were studied in human ovarian cancer cell line 3AO cells. Inhibition of cellular growth of 3AO cells was seen with E2 at concentrations higher than 0.1 μmol/L. The estrogen receptor inhibitor ICI 182780 cannot block the inhibitory effect of E2. It was surprising to find that ICI 182780 itself can inhibit the growth of 3AO cells, and had a collaborative effect with E2. The decreased cell growth induced by E2 was shown to be apoptosis as analyzed by flow cytometry. ERβ was detected in the 3AO ovarian cancer cell line but not ERα. The expression of ERβ was weak, which may partially explain why high but not low dose of E2 needed to induce the apoptosis of 3AO cells. We also observed that membrane impermeable E2, E2-BSA have lost growth inhibitory on 3AO cells, which excluded the membrane effect of E2 as previously reported by many investigators. The p38 kinase inhibitor, SB203580 were partially protected 3AO cells against growth inhibition by E2, while inhibitor of JNK, SP600125 enhanced cell death induced by E2. These results showed that MAPK is implicated in cellular processes involving apoptosis.</p></div>\",\"PeriodicalId\":100017,\"journal\":{\"name\":\"Acta Genetica Sinica\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":0.0000,\"publicationDate\":\"2006-09-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://sci-hub-pdf.com/10.1016/S0379-4172(06)60111-X\",\"citationCount\":\"5\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Acta Genetica Sinica\",\"FirstCategoryId\":\"1085\",\"ListUrlMain\":\"https://www.sciencedirect.com/science/article/pii/S037941720660111X\",\"RegionNum\":0,\"RegionCategory\":null,\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"\",\"JCRName\":\"\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Acta Genetica Sinica","FirstCategoryId":"1085","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S037941720660111X","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"","JCRName":"","Score":null,"Total":0}
引用次数: 5

摘要

近二十年来,对雌激素在不同组织和器官中发挥各种功能的分子机制的认识发展迅速。最近的报告表明,雌激素可以减少几种类型的癌细胞的细胞生长,包括卵巢癌细胞。虽然实验探索了抑制作用的可能机制,但其确切机制尚不清楚。卵巢是雌激素的主要来源,雌激素受体表达于卵巢的几种细胞类型中,包括卵巢表面上皮,约90%的卵巢癌起源于该组织。分析17β-雌二醇(E2)对卵巢癌细胞凋亡的影响,鉴定E2调控的参与上皮细胞增殖凋亡的特异性基因,可能为了解卵巢癌的进展和设计新的靶向治疗提供线索。为了阐明其中的机制,我们研究了雌激素药理浓度对人卵巢癌细胞系3AO细胞的影响。浓度大于0.1 μmol/L的E2对3AO细胞的生长有抑制作用。雌激素受体抑制剂ICI 182780不能阻断E2的抑制作用。令人惊讶的是,ICI 182780本身可以抑制3AO细胞的生长,并且与E2具有协同作用。流式细胞术分析显示E2诱导的细胞生长下降为细胞凋亡。3AO卵巢癌细胞系中检测到ERβ,但未检测到ERα。ERβ的表达较弱,这可能部分解释了为什么需要高剂量而不是低剂量E2才能诱导3AO细胞凋亡。我们还观察到膜不渗透性E2、E2- bsa对3AO细胞失去了生长抑制作用,这就排除了许多研究者之前报道的E2的膜效应。p38激酶抑制剂SB203580部分保护3AO细胞免受E2的生长抑制,而JNK抑制剂SP600125增强E2诱导的细胞死亡。这些结果表明MAPK参与细胞凋亡过程。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Effects of Pharmacological Concentrations of Estrogens on Growth of 3AO Human Ovarian Cancer Cells

During the past two decades, the knowledge of the molecular mechanism by which estrogens exert various functions in different tissues and organs has evolved rapidly. Recent reports demonstrated that estrogen could decrease the cell growth in several types of cancer cells, including ovarian cancer cells. Though experiments explored the possible mechanism of the inhibitory effect, the exact mechanism is responsible for the effect, which remains unclear. The ovary is the main source of the estrogen, estrogen receptor is expressed in several ovarian cell types, including ovarian surface epithelium, the tissue of origin of approximately 90% of the ovarian cancers. It was of great interest to analyze the effects of 17β-estradiol (E2) on apoptosis of ovarian cancer cells, and the identification of E2-regulated specific genes involved in epithelial proliferation apoptosis, thus may be a clue for understanding the progression of ovarian cancer and for the design of new target therapies. To elucidate the mechanism involved, effects of pharmacological concentrations of estrogen were studied in human ovarian cancer cell line 3AO cells. Inhibition of cellular growth of 3AO cells was seen with E2 at concentrations higher than 0.1 μmol/L. The estrogen receptor inhibitor ICI 182780 cannot block the inhibitory effect of E2. It was surprising to find that ICI 182780 itself can inhibit the growth of 3AO cells, and had a collaborative effect with E2. The decreased cell growth induced by E2 was shown to be apoptosis as analyzed by flow cytometry. ERβ was detected in the 3AO ovarian cancer cell line but not ERα. The expression of ERβ was weak, which may partially explain why high but not low dose of E2 needed to induce the apoptosis of 3AO cells. We also observed that membrane impermeable E2, E2-BSA have lost growth inhibitory on 3AO cells, which excluded the membrane effect of E2 as previously reported by many investigators. The p38 kinase inhibitor, SB203580 were partially protected 3AO cells against growth inhibition by E2, while inhibitor of JNK, SP600125 enhanced cell death induced by E2. These results showed that MAPK is implicated in cellular processes involving apoptosis.

求助全文
通过发布文献求助,成功后即可免费获取论文全文。 去求助
来源期刊
自引率
0.00%
发文量
0
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
确定
请完成安全验证×
copy
已复制链接
快去分享给好友吧!
我知道了
右上角分享
点击右上角分享
0
联系我们:info@booksci.cn Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。 Copyright © 2023 布克学术 All rights reserved.
京ICP备2023020795号-1
ghs 京公网安备 11010802042870号
Book学术文献互助
Book学术文献互助群
群 号:481959085
Book学术官方微信