苑辉卿
主要从事天然产物抗前列腺癌的分子药理学、前列腺癌相关基因的表达调控研究。
个性化签名
- 姓名:苑辉卿
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学术头衔:
博士生导师
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学科领域:
生物化学
- 研究兴趣:主要从事天然产物抗前列腺癌的分子药理学、前列腺癌相关基因的表达调控研究。
苑辉卿,女,1965年8月出生。生物化学与分子生物学专业教授,博士生导师。1986年6月毕业于山东医科大学药学系,获医学学士学位;1991年6月获山东医科大学天然药物化学专业硕士学位,2005年6获山东大学生物化学与分子生物学专业博士学位。1997年7月-1999年3月、2000年3月-6月在日本工业技术研究院产业技术融合领域研究所从事天然产物及高分子化合物对脂质体膜的稳定性。2003年3月-2004年3月在美国Mayo Clinic泌尿研究系Dr.Young实验室进行天然药物对前列腺癌细胞中雄激素受体调控的分子生物学研究。现主要从事天然产物抗前列腺癌的分子药理学、前列腺癌相关基因的表达调控研究。
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苑辉卿, Hui-Qing Yuan a, , Feng Kong a, Xiao-Ling Wanga, Charles Y.F. Young b, Xiao-Yan Hua, Hong-Xiang Lou c, *
biochemical pharmacology 75(2008)2112-2121,-0001,():
-1年11月30日
Androgen receptor (AR)-mediated signaling is crucial for the development and progression of prostate cancer (PCa). Naturally occurring phytochemicals that target the AR signaling offer significant protection against this disease. Acetyl-11-keto-b-boswellic acid (AKBA), a compound isolated from the gum-resin of Boswellia carterii, caused G1-phase cell cycle arrest with an induction of p21WAF1/CIP1, and a reduction of cyclin D1 as well in prostate cancer cells. AKBA-mediated cellular proliferation inhibition was associated with a decrease of AR expression at mRNA and protein levels. Furthermore, the functional biomarkers used in evaluation of AR transactivity showed suppressions of prostate-specific antigen promoterdependent and androgen responsive element-dependent luciferase activities. Additionally, down-regulation of an AR short promoter mainly containing a Sp1 binding site suggested the essential role of Sp1 for the reduction of AR expression in cells exposed to AKBA. Interruption effect of AKBA on Sp1 binding activity but not Sp1 protein levels was further confirmed by EMSA and transient transfection with a luciferase reporter driven by three copies of the Sp1 binding site of the AR promoter. Therefore, anti-AR properties ascribed to AKBA suggested that AKBA-containing drugs could be used for the development of novel therapeutic chemicals.
Acetyl-11-keto-b-boswellic acid, Cell cycle arrest, Androgen receptor, Sp1, Prostate cancer cell lines
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【期刊论文】PSA启动子介导的TAT-P21WAF1/CIP1融合蛋白在前列腺癌细胞中的特异表达及活性初探*
苑辉卿, 蔡捷, 孔峰, 任凯, 王小玲, 吉恺, 胡晓燕, 张建业
中国病理生理杂志,2008,24(3):498~503,-0001,():
-1年11月30日
目的:设计并构建含有前列腺组织特异性抗原(PSA)启动子的TAT-p21WAF1/CIP1融合蛋白真核表达载体(pPSA-TAT-p21),使由TAT蛋白转导结构域(TAT)介导的抑癌基因蛋白TAT-p21WAF1/CIP1(p21)能够在前列腺癌细胞中实现特异性的跨膜转运,增强p2l对前列腺癌的抑制作用。方法:利用PCR技术构建含有PSA启动子、TAT蛋白转导序列和p2l读码框架的真核表达载体pPSA-TAT-p2l,并进行酶切、测序鉴定。脂质体法在前列腺癌LNCaP细胞和大肠癌HT-29细胞中转染上述表达载体及对照质粒后进行反转录pCR(RT-PCR),检测p21的mRNA以及蛋白在不同细胞中的表达情况。MTr法检测转染pPSA-TAT-p2l后LNCaP细胞的增殖情况。结果:成功构建pPSA-TAT-p2l真核表达载体。RT-PCR和Western hotting结果显示PSA-TAT-p2l在前列腺癌细胞中有明显表达,在大肠癌细胞中基本不表达,呈现特异性的表达,而由CMV启动子介导的p2l(pCMV-21)对照组在两个细胞株中均有表达。细胞增殖实验结果显示,含有TAT蛋白转导结构域的PSA-TAT-p21的融合蛋白对前列腺癌细胞增殖的抑制作用明显高于不含TAT的PSA-p2l蛋白。结论:pPSA-TAT-p21能够在前列腺癌细胞中特异性地高效表达,为前列腺癌基因的靶向治疗提供了实验依据。
前列腺特异抗原, FAT-p21WAF1/, CIP1融合蛋白, 前列腺肿瘤, LNCaP细胞, HT-29细胞
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【期刊论文】Cycloartane-Type Triterpenoids from the Resinous Exudates of Commiphora opobalsamum
苑辉卿, Tao Shen, † Hui-Qing Yuan, ‡ Wen-Zhu Wan, † Xiao-Ling Wang, ‡ Xiao-Ning Wang, † Mei Ji, † and Hong-Xiang Lou*, †
J. Nat. Prod. 2008, 71, 81-86,-0001,():
-1年11月30日
Eight new cycloartane-type triterpenoids, cycloartan-24-ene-1R, 2R, 3R-triol (1), 3β-acetoxycycloartan-24-ene-1R, 2R-diol (2), 1R-acetoxycycloartan-24-ene-2R, 3β-diol (3), 3β-isovaleroyloxycycloartan-24-ene-1R, 2R-diol (4), cycloartan-24-ene-1R, 3β-diol (5), cycloartan-23E-ene-1R, 2R, 3β, 25-tetrol (6), and an epimeric mixture of 24R, 25-epoxycycloartane-1R, 2R, 3β-triol (7) and 24S, 25-epoxycycloartane-1R, 2R, 3β-triol (8), together with one known compound, cycloartan-24-ene-1R, 2R, 3β-triol (9), were isolated from the resinous exudates of Commiphora opobalsamum. Their structures were established on the basis of mass spectrometry and multidimensional NMR spectroscopy. The cytotoxicity of compounds 1–9 was evaluated against the PC3 and DU145 human prostate tumor cell lines. All of the compounds except 1 and 5 exhibited moderate cytotoxicity against PC3 or DU145 cells with IC50 values ranging from 10.1 to 37.2μM.
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【期刊论文】鞘脂激活肽真核表达载体的构建及其对前列腺癌细胞增殖的影响
苑辉卿, 任凯, 孔峰, 蔡捷, 王小玲, 胡晓燕, 徐霞, 张建业
山东大学学报(医学版),2007,45(1):1~7,-0001,():
-1年11月30日
目的:构建含有鞘脂激活蛋白原神经营养序列短肽-鞘脂激活肽NP(neurotrophic peptide,NP)的真核表达载体以及NP与TAT的融合蛋白真核表达载体(TAT-NP),探讨NP在前列腺癌细胞中的作用。方法:根据NP和TAT的氨基酸序列合成其DNA序列,利用基因克隆技术构建含有TAT和NP读码框架的真核表达载体pcDNA-TAT-NP和pcDNA-NP。在前列腺癌PC3、LNCaP细胞中转染上述载体后通过RT-PCR、MTT和流式细胞术,分别检测TAT-NP、NP的mRNA的表达,NP对前列腺瘤细胞的增殖情况以及对细胞周期的影响。结果:经测序鉴定,成功构建pcDNA-TAT-NP和pcDNA-NP真核表达载体。RT-PCR结果显示,TAT-NP、NP能够在前列腺癌细胞中表达。MTT结果表明,TAT-NP、NP均对前列腺癌细胞增殖具有促进作用。流式细胞结果显示,TAT-NP、NP具有促进细胞进入S和G2/M期的作用。结论:外源表达的鞘脂激活肽NP能够促进前列腺癌细胞的增殖,并能影响细胞周期各时相的变化。
鞘脂激活蛋白原, 鞘脂激活肽, TAT蛋白转导结构域, 流式细胞术, 前列腺肿瘤, 细胞株
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苑辉卿, Mei-Lan He, M.D., Hui-Qing Yuan, Ph.D., An-Li Jiang, Ai Yu Gong, M.Sc., Wei-Wen Chen, Peng-Ju Zhang, Charles Y. F. Young, Jian-Ye Zhang
Cancer 2006; 106: 2547-55,-0001,():
-1年11月30日
Accumulating evidence suggests that the androgen receptor (AR) may play an important role in the development and progression of prostate cancer. To find new, useful compounds that effectively may attenuate the function of AR in prostate cancer cells, the authors investigated the effect of gum mastic, a natural resin, on AR activity. An androgen-responsive prostate cancer cell line LNCaP was used as a model for this study. Gene transfer, reverse transcriptase-polymerase chain reaction analysis, electrophoretic mobility shift assay, and Western blot analysis were used to test the effect of gum mastic on the expression and function of the AR. To demonstrate the inhibitory effect of gum mastic on the function of the AR, the expression of androgen-regulated genes, including prostate-specific antigen (PSA), human kallikrein 2 (hK2), and NKX3.1 were measured. In addition, transient transfection assays with the PSA promoter and the AR promoter also were used to test the effects of mastic. The results showed that gum mastic inhibited the expression of the AR at the transcriptional level, resulting in the down-regulation of both AR messenger RNA and protein levels. Therefore, the function of the AR was inhibited, as reflected by the reduced expression of NKX3.1 and PSA and by androgen-stimulated growth. Because gum mastic exhibited a strong in vitro potency to attenuate the expression and function of the AR, further investigation will be required to determine whether this naturally occurring substance has in vivo potency to inhibit prostate cancer development.
gum mastic,, androgen receptor,, androgen-regulated gene,, prostate cancer cell line
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苑辉卿, Yuan H, Gong A, Young CY.
,-0001,():
-1年11月30日
The transactivation function of the human androgen receptor (AR) can be regulated by several coregulators that may be either positive or negative. Ubiquitous transcription factor Sp1 not only regulates the basal expression of the AR but also acts as its co-regulator. Our previous study has shown that quercetin, one of the main polyphenols, can effectively inhibit the expression and function of the AR. The present study is to address if quercetin may affect Sp1's function on AR transactivation activity in human prostate adenocarcinoma cell lines, LNCaP and PC-3. First we showed that indeed in transient transfections Sp1 could enhance transcriptional activity of the AR promoter and of androgen up-regulated gene promoters, i.e., the prostate-specific antigen and the hK2 genes. Interestingly, the enhancing activity of Sp1 could be repressed by quercetin. The gel shift and western blot analyses indicated that the specific DNA motif binding activity of Sp1 and its protein levels were not altered by quercetin. However, the state of interaction of Sp1 with the AR treated by quercetin plus androgen was different from that by androgen treatment or none as demonstrated by co-immunoprecipitation experiments and GST pull-down assays. Moreover, we showed that quercetin caused changes in post-translational modification of AR protein. The above findings strongly suggest that changes induced by quercetin in post-translational modification of the AR and in states of physical interaction of Sp1 with the AR may be critical for the attenuation of AR's function.
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【期刊论文】槲皮素对前列腺癌细胞增殖及转录因子Sp1功能的抑制作用
苑辉卿, 苑辉卿), 杨玲玲), 姜安丽), 孔峰), 张建业)*Charles Y F YOUNG)*
中国生物化学与分子生物学报,2005,21(5):673~378,-0001,():
-1年11月30日
雄激素受体(androgen receptor,AR)作为核转录因子,其高表达、基因突变以及AR辅激活因子的过表达等造成AR的异常激活与前列腺癌细胞的增殖、恶化转移、多药耐药等密切相关。天然黄酮槲皮素(quereetin),是一很有潜力的预防和治疗前列腺肿瘤的化合物。槲皮素不仅抑制前列腺癌细胞LNcaP的增殖,并呈剂量依赖性,而且下调前列腺癌中AR的表达、抑制AR的转录激活功能。GC box是AR核心启动子的主要正调控元件,是转录因子Spl的结合位点。细胞转染结果表明,槲皮素能抑制Spl蛋白对AR启动子的激活作用,可能是槲皮素下调AR表达的机理之一。进一步研究显示,槲皮素还能明显抑制Spl蛋白对AR转录激活功能的增强作用。Western印迹结果显示,槲皮素对Spl蛋白表达无明显影响,但能够诱导c-Jun的高表达,而高表达的c-Jun蛋白能逆转Spl蛋白对AR的转录激活作用,由此推测,槲皮素可能通过介导c-Jun与spl的蛋白质相互作用,抑制spl的功能,进而起到抑制AR表达和功能的作用。免疫沉淀结果又进一步证实了Spl与c-Jun二者的相互作用。因此,槲皮素可能通过抑制前列腺癌细胞中AR的表达和功能抑制了细胞的增殖,其分子机理可能与槲皮素诱导的c-Jun与Spl蛋白相互作用、降低Spl对AR的转录激活作用有关。
槲皮素,, 细胞增殖,, Spl,, 前列腺癌细胞,, 抑制作用
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苑辉卿, Huiqing Yuan a, b, Yunqian Pan a, Charles Y.F. Young a, *
Cancer Letters 213(2004)155-163,-0001,():
-1年11月30日
Previously, we reported that quercetin and resveratrol inhibit the function of androgen receptor (AR). Further studies showed that these two polyphenols caused an increase in expression of c-Jun as well as its phosphorylated form in a dose-dependent manner in prostatic cell lines. Gel shift assay showed that induced c-Jun has specific DNA binding activity. Transient transfections demonstrated that c-Jun repressed prostate-specific antigen promoter activity and transcriptional activity of the AR promoter. These results support a mechanism in which overexpressed c-Jun mediates inhibitory effect on the function of AR. These polyphenols might potentially be useful in prostate cancer prevention.
c-Jun, Androgen receptor, Quercetin, Resveratrol, Prostate cancer cell lines
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【期刊论文】Polyphenols from peanut skins and their free radical-scavenging effects
苑辉卿, Hongxiang Lou a, *, Huiqing Yuan b, Bin Ma a, Dongmei Ren a, Mei Ji a, Syuichi Oka c
Phytochemistry 65(2004)2391-2399,-0001,():
-1年11月30日
Separation of the water-soluble fraction of peanut skins led to the isolation of five proanthocyanidins. Based on the spectroscopic investigation and partial acid catalyzed degradation, their structures were determined to be epicatechin-(2β→O→7, 4β→6)-[epicatechin-(4β→8)]-catechin (1), epicatechin-(2β→O→7, 4β→8) epicatechin-(4β→8)-catechin-(4α→8)-epicatechin (2), and procyanidins B2 (3), B3 (4) and B4 (5). The absolute configuration of the new compounds was determined from their circular dichroism curves and the 1H NMR spectra of analysis of flavan-3-ols formed by thiolytic degradation of 1 and 2 in the presence of a chiral dirhodium complex (dirhodium tetra-(R-(trifluoromethyl) phenyl acetate).
Arachis hypogaea, Leguminosae, Peanut skin, Proanthocyanidins
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