卡马西平对雌激素依赖性乳腺癌细胞增殖的抑制作用及其机制的研究
R737.9; 背景与目的:卡马西平是一种应用多年的抗癫痫药,最近研究证明其具有组蛋白脱乙酰化酶抑制剂(histone deacetylase inhibitor,HDI)的性质.而已知的HDI多具有抗肿瘤作用.本实验旨在探讨卡马西平对雌激素受体α(estrogen receptor α,ERα)阳性乳腺癌细胞增殖的抑制作用及其机制.方法:利用磺酰罗丹明B色度法(sulforhodamine B,SRB)分析不同情况下卡马西平对细胞增殖的影响.Western blot法检测ERα、Cyclin D1等相关蛋白的表达水平;RT-PCR法检测相应mRNA水平的变化;免疫荧光法测定他莫昔芬耐药细胞M...
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| Published in | 癌症 Vol. 25; no. 8; pp. 967 - 973 |
|---|---|
| Main Authors | , , , , , |
| Format | Journal Article |
| Language | Chinese |
| Published |
哈尔滨医科大学附属肿瘤医院内四科,黑龙江,哈尔滨,150040%哈尔滨医科大学病理生理教研室,黑龙江,哈尔滨,150086
2006
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| Subjects | |
| Online Access | Get full text |
| ISSN | 1000-467X |
| DOI | 10.3321/j.issn:1000-467X.2006.08.008 |
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| Abstract | R737.9; 背景与目的:卡马西平是一种应用多年的抗癫痫药,最近研究证明其具有组蛋白脱乙酰化酶抑制剂(histone deacetylase inhibitor,HDI)的性质.而已知的HDI多具有抗肿瘤作用.本实验旨在探讨卡马西平对雌激素受体α(estrogen receptor α,ERα)阳性乳腺癌细胞增殖的抑制作用及其机制.方法:利用磺酰罗丹明B色度法(sulforhodamine B,SRB)分析不同情况下卡马西平对细胞增殖的影响.Western blot法检测ERα、Cyclin D1等相关蛋白的表达水平;RT-PCR法检测相应mRNA水平的变化;免疫荧光法测定他莫昔芬耐药细胞MCF-7RT中HER-2的表达;免疫沉淀技术检测Hsp90的分子伴侣功能及乙酰化水平.结果:卡马西平处理ERα阳性细胞MCF-7及T47D时,显著抑制雌二醇刺激的细胞增殖效应(P＜0.01);卡马西平与4羟基他莫昔芬(4-OHT)联合处理MCF-7细胞,对雌二醇引起的细胞增殖抑制呈相加作用(q=1.00);在MCF-7RT细胞中,卡马西平逆转了4-OHT的刺激增殖作用(P＜0.01);卡马西平处理可以降低ERα阳性细胞中ERα、Cyclin D1在蛋白及mRNA水平的表达,并降低MCF-7RT细胞中HER-2表达;ERα、Cyclin D1的表达降低可以被26s蛋白酶体抑制剂MG132抑制;卡马西平可以促进Hsp90乙酰化并破坏其分子伴侣功能.结论:卡马西平明显抑制ER阳性乳腺癌细胞增殖,该作用可能部分通过促进ERα、Cyclin D1的蛋白酶体降解途径实现.卡马西平可以通过降低HER-2表达逆转与HER-2相关的4-OHT耐药. |
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| AbstractList | R737.9; 背景与目的:卡马西平是一种应用多年的抗癫痫药,最近研究证明其具有组蛋白脱乙酰化酶抑制剂(histone deacetylase inhibitor,HDI)的性质.而已知的HDI多具有抗肿瘤作用.本实验旨在探讨卡马西平对雌激素受体α(estrogen receptor α,ERα)阳性乳腺癌细胞增殖的抑制作用及其机制.方法:利用磺酰罗丹明B色度法(sulforhodamine B,SRB)分析不同情况下卡马西平对细胞增殖的影响.Western blot法检测ERα、Cyclin D1等相关蛋白的表达水平;RT-PCR法检测相应mRNA水平的变化;免疫荧光法测定他莫昔芬耐药细胞MCF-7RT中HER-2的表达;免疫沉淀技术检测Hsp90的分子伴侣功能及乙酰化水平.结果:卡马西平处理ERα阳性细胞MCF-7及T47D时,显著抑制雌二醇刺激的细胞增殖效应(P＜0.01);卡马西平与4羟基他莫昔芬(4-OHT)联合处理MCF-7细胞,对雌二醇引起的细胞增殖抑制呈相加作用(q=1.00);在MCF-7RT细胞中,卡马西平逆转了4-OHT的刺激增殖作用(P＜0.01);卡马西平处理可以降低ERα阳性细胞中ERα、Cyclin D1在蛋白及mRNA水平的表达,并降低MCF-7RT细胞中HER-2表达;ERα、Cyclin D1的表达降低可以被26s蛋白酶体抑制剂MG132抑制;卡马西平可以促进Hsp90乙酰化并破坏其分子伴侣功能.结论:卡马西平明显抑制ER阳性乳腺癌细胞增殖,该作用可能部分通过促进ERα、Cyclin D1的蛋白酶体降解途径实现.卡马西平可以通过降低HER-2表达逆转与HER-2相关的4-OHT耐药. |
| Author | 赵长宏 孟庆威 蔡莉 席玉慧 隋广杰 孙立春 |
| AuthorAffiliation | 哈尔滨医科大学附属肿瘤医院内四科,黑龙江,哈尔滨,150040%哈尔滨医科大学病理生理教研室,黑龙江,哈尔滨,150086 |
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| Author_FL | CAI Li ZHAO Chang-Hong XI Yu-Hui SUN Li-Chun MENG Qing-Wei SUI Guang-Jie |
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| Keywords | 乳腺肿瘤 卡马西平 MCF-7细胞 雌激素受体α T47D细胞 细胞周期素D1 他莫昔芬 |
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| Snippet | R737.9; 背景与目的:卡马西平是一种应用多年的抗癫痫药,最近研究证明其具有组蛋白脱乙酰化酶抑制剂(histone deacetylase inhibitor,HDI)的性质.而已知的HDI多具有抗肿瘤作... |
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| Title | 卡马西平对雌激素依赖性乳腺癌细胞增殖的抑制作用及其机制的研究 |
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