类固醇激素受体共活化因子3（SRC-3）在天然药物治疗恶性血液病中的意义
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摘要
第一部分
藤黄酸抑制类固醇激素受体共活化因子3及Akt通路介导慢性粒细胞白血病急变K562细胞株G0／G1期阻滞和凋亡
目的：研究藤黄酸抗白血病的影响及其分子机制，为其临床应用提供理论基础。
方法：采用MTT比色法检测K562细胞的增殖活性，Annexin V-FITC／PI双标法检测细胞凋亡及透射电镜分析细胞凋亡形态学的改变，流式细胞术分析细胞周期改变，Realtime-PCR检测藤黄酸对K562细胞内SRC-3和Bcl-2基因表达的影响，Western blot法检测藤黄酸对K562细胞内SRC-3，Akt，pAkt，核糖体蛋白S6激酶1(S6K1)，pS6K1，糖原合成激酶3β(GSK-3β)，pGSK-3β和Bcl-2蛋白表达的影响。
结果：(1)藤黄酸以剂量、时间依赖性方式抑制K562细胞的增殖，其24 h的IC50是1．9±0．1μmol／L。(2)藤黄酸以剂量依赖性方式诱导K562细胞凋亡，伴有典型的凋亡细胞形态学改变。(3)藤黄酸阻滞K562细胞周期于G0／G1期。(4)藤黄酸能以剂量依赖性方式抑制SRC-3，pAkt，pS6K1，pGSK-3β和Bcl-2表达水平，而Akt，S6K1和GSK-3β总蛋白水平不受影响。
结论：藤黄酸发挥其抗白血病效应可能与下调类固醇激素受体共活化因子3(SRC-3)的表达有关。
第二部分
鱼藤素抑制类固醇激素受体共活化因子3及NF-κB通路介导急性淋巴细胞白血病Jurkat细胞凋亡
目的：研究鱼藤素抗白血病的影响及其分子机制，为其临床应用提供理论基础。
方法：采用MTT比色法检测Jurkat细胞的增殖活性，原位细胞凋亡检测技术(TUNEL)及透射电镜分析细胞凋亡形态学的改变，流式细胞术分析细胞周期改变，RT-PCR和Westem blot法检测鱼藤素对白血病细胞内SRC-3，NF-κB，Bcl-2，Bcl-xL基因和蛋白表达的影响。
结果：(1)鱼藤素以剂量、时间依赖性方式抑制Jurkat细胞的增殖，其24 h的IC50是43．73±0．35 nmol／L，48h的IC50为28．96±0．29 nmol／L。(2)鱼藤素以剂量依赖性方式诱导Jurkat细胞凋亡。40 nmol／L的鱼藤素处理24 h后透射电镜观察到细胞染色质浓缩，核碎裂，典型凋亡小体形成。TUNEL法检测到TUNEL阳性细胞，40 nmol／L的鱼藤素处理24 h后TUNEL阳性细胞百分比为12．8±0．85％，与对照组(1．1±0．09％)相比有统计学意义(P＜0．01)；(3)鱼藤素阻滞Jurkat细胞周期于G0／G1期。(4)鱼藤素能同时在蛋白和基因水平，以剂量依赖性方式抑制SRC-3及其相关基因NF-κB和其下游的抗凋亡蛋白Bcl-2，Bcl-xL的表达。
结论：鱼藤素能明显抑制Jurkat白血病细胞的增殖，并诱导其凋亡，其抗白血病效应可能与下调类固醇激素受体共活化因子3(SRC-3)的表达有关。
第三部分
鱼藤素对多发性骨髓瘤细胞类固醇激素受体共活化因子3的调节作用
目的：研究鱼藤素对人多发性骨髓瘤细胞株RPMI-8226细胞抗增殖影响及其分子机制。
方法：采用MTT比色法检测鱼藤素对RPMI-8226细胞增殖活性的影响，Annexin-VFITC／PI双标法及Hoechst33258分析细胞凋亡形态学的改变，肿瘤细胞侵袭实验检测鱼藤素对RPMI-8226细胞侵袭作用的影响，RT-PCR法检测鱼藤素对SRC-3和NF-κB基因表达的影响，免疫组化法检测鱼藤素对SRC-3和NF-κB蛋白的影响和分布情况，明胶酶法用来检测RPMI-8226细胞分泌MMP-2和MMP-9酶的活性。
结果：(1)鱼藤素能明显抑制RPMI 8226细胞的增殖，其24 h的IC_(50)是54．55±0．40nmol／L。(2)鱼藤素以剂量依赖性方式诱导RPMI-8226细胞凋亡，伴有典型的凋亡细胞形态学改变。(3)鱼藤素能以剂量依赖性方式抑制RPMI-8226细胞侵袭。(4)鱼藤素能同时在蛋白和基因水平抑制SRC-3及其相关基因NF-κB，从而下调MMP-2和MMP-9酶的活性。
结论：鱼藤素发挥其抗多发性骨髓瘤效应可能与下调SRC-3的表达有关。
PartⅠ
Gambogic acid induces G0/G1 arrest and apoptosisinvolving inhibition of SRC-3 and inactivation of Aktpathway in K562 leukemia cells
Objective:To investigate the anticancer effects and the molecular mechanisms ofGambogic acid(GA) on K562 cells and to provide more theories for clinical application.
Methods:The effects of Gambogic acid on the growth ofK562 cells were studied by MTTassay.Annexin V/PI double-labeled cytometry and transmission electron microscopy wereused to detect cell apoptosis.A propidium iodide method was used to study cell cycledistribution.Quantitative real-time PCR was employed to assess the expression levels ofsteroid receptor coactivator-3 (SRC-3) and apoptosis related gene Bcl-2.Western blottingwas employed to assess the expression levels of SRC-3,Akt,pAkt,S6K1,pS6K1,GSK-3β,pGSK-3βand Bcl-2.
Results:(1) GA was able to inhibit cell proliferation in K562 cells in a time- and dose-dependent manner,with 24h IC_(50) value of 1.9±0.1μmol/L.(2) Gambogic acid inducedapoptosis of K562 cells in a dose-dependent manner,which was accompanied by typicalapoptotic morphological changes.(3) GA induced cell-cycle arrest in G0/G1 phase in K562cells.(4) GA treatment downregulated the expression of SRC-3 and inhibited the activity ofAkt kinase and its downstream targets p70 S6 kinase 1 (S6K1) and glycogen synthasekinase 3β(GSK-3β) without changes in total protein levels of these three proteins in K562cells,accompanied by decreased expression of the apoptosis related gene Bcl-2.
Conclusion:GA might exhibit its strong antitumor effects via the interruption of SRC-3.
PartⅡ
Deguelin induces apoptosis involving inhibition of SRC-3 andNF-κB pathway in Jurkat cells
Objective:To investigate the anticancer effects and the molecular mechanisms of deguelin onJurkat cells and to provide more theories for clinical application.
Methods:The effects of deguelin on the growth of Jurkat cells were studied by MTT assay.Terminal deoxynucleotide transferase-mediated dUTP nick end labeling (TUNEL) assay andtransmission electron microscopy were used to detect cell apoptosis.A propidium iodidemethod was used to study cell cycle distribution.RT-PCR and western blotting were employedto assess the expression levels of steroid receptor coactivator-3 (SRC-3),nuclear factor-κB(NF-κB) and some apoptosis related genes,including Bcl-2 and Bcl-xL.
Results:(1) Deguelin was able to inhibit cell proliferation in Jurkat cells in a time- anddose-dependent manner,with 24h IC_(50) value of 43.73±0.35 nmol/L and 48h IC_(50) value of28.96±0.29 nmol/L.(2) Deguelin induced apoptosis in Jurkat cells in a dose-dependentmanner in vitro.After treatment with 40nmol/l deguelin for 24h,apoptotic bodies containingnuclear fragments and the chromatin condensed were found by Transmission electronmicroscopy.Jurkat cells treated with 40nmol/l deguelin for 24h also showed positive TUNELstaining.The percentage of TUNEL positive cells was 12.8±0.85%,compared with only 1.1±0.09% TUNEL positive cells in the untreated samples (P＜0.01).(3) Deguelin induced cell-cycle arrest in G0/G1 phase in Jurkat cells.(4) Deguelin could downregulate theexpression of SRC-3 and its downstream transcription factor NF-κB,which thus influencedthe expression of apoptosis related genes Bcl-2 and Bcl-xL.
Conclusion:Deguelin presents potent effects on growth-arrest and apoptosis-induction inJurkat cells in vitro via the interruption of SRC-3.
PartⅢ
Effects of deguelin on the regulation of SRC-3 in MM cells in vitro
Objective:To investigate the anticancer effects and the molecular mechanisms of deguelin onRPMI-8226 cells.
Methods:The effects of deguelin on the growth of RPMI-8226 cells were studied by MTTassay.Hoechst 33258 staining and Annexin-V FITC/PI double-labeled cytometry wereused to detect cell apoptosis.Transwell invasion assay was used to assess the role ofdeguelin on RPMI-8226 cell invasion.RT-PCR was employed to assess the mRNAexpression levels of SRC-3 and NF-κB,whereas,SRC-3 and NF-κB protein expression andlocalization were determined by using immunohistochemistry method.GelatinZymography was used to detect the gelatinolytic activity of secreted MMP-2 and -9.
Results:(1) Deguelin presented striking proliferation inhibition potency on RPMI-8226cells in vitro,with 24h IC50 value of 54.55±0.40nmol/L.(2) Deguelin induced apoptosis inRPMI-8226 cells in a dose-dependent manner in vitro,which was accompanied by typicalapoptotic morphological changes.(3) Deguelin could inhibit RPMI-8226 cell invasion.(4)Deguelin could downregulate the expression of SRC-3 and its downstream transcriptionfactor NF-κB,which thus influenced the gelatinolytic activity of secreted MMP-2 and -9.
Conclusion:Deguelin exhibit its strong antitumor effects via the interruption of SRC-3.
藤黄酸抑制类固醇激素受体共活化因子3及Akt通路介导慢性粒细胞白血病急变K562细胞株G0／G1期阻滞和凋亡
目的：研究藤黄酸抗白血病的影响及其分子机制，为其临床应用提供理论基础。
方法：采用MTT比色法检测K562细胞的增殖活性，Annexin V-FITC／PI双标法检测细胞凋亡及透射电镜分析细胞凋亡形态学的改变，流式细胞术分析细胞周期改变，Realtime-PCR检测藤黄酸对K562细胞内SRC-3和Bcl-2基因表达的影响，Western blot法检测藤黄酸对K562细胞内SRC-3，Akt，pAkt，核糖体蛋白S6激酶1(S6K1)，pS6K1，糖原合成激酶3β(GSK-3β)，pGSK-3β和Bcl-2蛋白表达的影响。
结果：(1)藤黄酸以剂量、时间依赖性方式抑制K562细胞的增殖，其24 h的IC50是1．9±0．1μmol／L。(2)藤黄酸以剂量依赖性方式诱导K562细胞凋亡，伴有典型的凋亡细胞形态学改变。(3)藤黄酸阻滞K562细胞周期于G0／G1期。(4)藤黄酸能以剂量依赖性方式抑制SRC-3，pAkt，pS6K1，pGSK-3β和Bcl-2表达水平，而Akt，S6K1和GSK-3β总蛋白水平不受影响。
结论：藤黄酸发挥其抗白血病效应可能与下调类固醇激素受体共活化因子3(SRC-3)的表达有关。
第二部分
鱼藤素抑制类固醇激素受体共活化因子3及NF-κB通路介导急性淋巴细胞白血病Jurkat细胞凋亡
目的：研究鱼藤素抗白血病的影响及其分子机制，为其临床应用提供理论基础。
方法：采用MTT比色法检测Jurkat细胞的增殖活性，原位细胞凋亡检测技术(TUNEL)及透射电镜分析细胞凋亡形态学的改变，流式细胞术分析细胞周期改变，RT-PCR和Westem blot法检测鱼藤素对白血病细胞内SRC-3，NF-κB，Bcl-2，Bcl-xL基因和蛋白表达的影响。
结果：(1)鱼藤素以剂量、时间依赖性方式抑制Jurkat细胞的增殖，其24 h的IC50是43．73±0．35 nmol／L，48h的IC50为28．96±0．29 nmol／L。(2)鱼藤素以剂量依赖性方式诱导Jurkat细胞凋亡。40 nmol／L的鱼藤素处理24 h后透射电镜观察到细胞染色质浓缩，核碎裂，典型凋亡小体形成。TUNEL法检测到TUNEL阳性细胞，40 nmol／L的鱼藤素处理24 h后TUNEL阳性细胞百分比为12．8±0．85％，与对照组(1．1±0．09％)相比有统计学意义(P＜0．01)；(3)鱼藤素阻滞Jurkat细胞周期于G0／G1期。(4)鱼藤素能同时在蛋白和基因水平，以剂量依赖性方式抑制SRC-3及其相关基因NF-κB和其下游的抗凋亡蛋白Bcl-2，Bcl-xL的表达。
结论：鱼藤素能明显抑制Jurkat白血病细胞的增殖，并诱导其凋亡，其抗白血病效应可能与下调类固醇激素受体共活化因子3(SRC-3)的表达有关。
第三部分
鱼藤素对多发性骨髓瘤细胞类固醇激素受体共活化因子3的调节作用
目的：研究鱼藤素对人多发性骨髓瘤细胞株RPMI-8226细胞抗增殖影响及其分子机制。
方法：采用MTT比色法检测鱼藤素对RPMI-8226细胞增殖活性的影响，Annexin-VFITC／PI双标法及Hoechst33258分析细胞凋亡形态学的改变，肿瘤细胞侵袭实验检测鱼藤素对RPMI-8226细胞侵袭作用的影响，RT-PCR法检测鱼藤素对SRC-3和NF-κB基因表达的影响，免疫组化法检测鱼藤素对SRC-3和NF-κB蛋白的影响和分布情况，明胶酶法用来检测RPMI-8226细胞分泌MMP-2和MMP-9酶的活性。
结果：(1)鱼藤素能明显抑制RPMI 8226细胞的增殖，其24 h的IC_(50)是54．55±0．40nmol／L。(2)鱼藤素以剂量依赖性方式诱导RPMI-8226细胞凋亡，伴有典型的凋亡细胞形态学改变。(3)鱼藤素能以剂量依赖性方式抑制RPMI-8226细胞侵袭。(4)鱼藤素能同时在蛋白和基因水平抑制SRC-3及其相关基因NF-κB，从而下调MMP-2和MMP-9酶的活性。
结论：鱼藤素发挥其抗多发性骨髓瘤效应可能与下调SRC-3的表达有关。
PartⅠ
Gambogic acid induces G0/G1 arrest and apoptosisinvolving inhibition of SRC-3 and inactivation of Aktpathway in K562 leukemia cells
Objective:To investigate the anticancer effects and the molecular mechanisms ofGambogic acid(GA) on K562 cells and to provide more theories for clinical application.
Methods:The effects of Gambogic acid on the growth ofK562 cells were studied by MTTassay.Annexin V/PI double-labeled cytometry and transmission electron microscopy wereused to detect cell apoptosis.A propidium iodide method was used to study cell cycledistribution.Quantitative real-time PCR was employed to assess the expression levels ofsteroid receptor coactivator-3 (SRC-3) and apoptosis related gene Bcl-2.Western blottingwas employed to assess the expression levels of SRC-3,Akt,pAkt,S6K1,pS6K1,GSK-3β,pGSK-3βand Bcl-2.
Results:(1) GA was able to inhibit cell proliferation in K562 cells in a time- and dose-dependent manner,with 24h IC_(50) value of 1.9±0.1μmol/L.(2) Gambogic acid inducedapoptosis of K562 cells in a dose-dependent manner,which was accompanied by typicalapoptotic morphological changes.(3) GA induced cell-cycle arrest in G0/G1 phase in K562cells.(4) GA treatment downregulated the expression of SRC-3 and inhibited the activity ofAkt kinase and its downstream targets p70 S6 kinase 1 (S6K1) and glycogen synthasekinase 3β(GSK-3β) without changes in total protein levels of these three proteins in K562cells,accompanied by decreased expression of the apoptosis related gene Bcl-2.
Conclusion:GA might exhibit its strong antitumor effects via the interruption of SRC-3.
PartⅡ
Deguelin induces apoptosis involving inhibition of SRC-3 andNF-κB pathway in Jurkat cells
Objective:To investigate the anticancer effects and the molecular mechanisms of deguelin onJurkat cells and to provide more theories for clinical application.
Methods:The effects of deguelin on the growth of Jurkat cells were studied by MTT assay.Terminal deoxynucleotide transferase-mediated dUTP nick end labeling (TUNEL) assay andtransmission electron microscopy were used to detect cell apoptosis.A propidium iodidemethod was used to study cell cycle distribution.RT-PCR and western blotting were employedto assess the expression levels of steroid receptor coactivator-3 (SRC-3),nuclear factor-κB(NF-κB) and some apoptosis related genes,including Bcl-2 and Bcl-xL.
Results:(1) Deguelin was able to inhibit cell proliferation in Jurkat cells in a time- anddose-dependent manner,with 24h IC_(50) value of 43.73±0.35 nmol/L and 48h IC_(50) value of28.96±0.29 nmol/L.(2) Deguelin induced apoptosis in Jurkat cells in a dose-dependentmanner in vitro.After treatment with 40nmol/l deguelin for 24h,apoptotic bodies containingnuclear fragments and the chromatin condensed were found by Transmission electronmicroscopy.Jurkat cells treated with 40nmol/l deguelin for 24h also showed positive TUNELstaining.The percentage of TUNEL positive cells was 12.8±0.85%,compared with only 1.1±0.09% TUNEL positive cells in the untreated samples (P＜0.01).(3) Deguelin induced cell-cycle arrest in G0/G1 phase in Jurkat cells.(4) Deguelin could downregulate theexpression of SRC-3 and its downstream transcription factor NF-κB,which thus influencedthe expression of apoptosis related genes Bcl-2 and Bcl-xL.
Conclusion:Deguelin presents potent effects on growth-arrest and apoptosis-induction inJurkat cells in vitro via the interruption of SRC-3.
PartⅢ
Effects of deguelin on the regulation of SRC-3 in MM cells in vitro
Objective:To investigate the anticancer effects and the molecular mechanisms of deguelin onRPMI-8226 cells.
Methods:The effects of deguelin on the growth of RPMI-8226 cells were studied by MTTassay.Hoechst 33258 staining and Annexin-V FITC/PI double-labeled cytometry wereused to detect cell apoptosis.Transwell invasion assay was used to assess the role ofdeguelin on RPMI-8226 cell invasion.RT-PCR was employed to assess the mRNAexpression levels of SRC-3 and NF-κB,whereas,SRC-3 and NF-κB protein expression andlocalization were determined by using immunohistochemistry method.GelatinZymography was used to detect the gelatinolytic activity of secreted MMP-2 and -9.
Results:(1) Deguelin presented striking proliferation inhibition potency on RPMI-8226cells in vitro,with 24h IC50 value of 54.55±0.40nmol/L.(2) Deguelin induced apoptosis inRPMI-8226 cells in a dose-dependent manner in vitro,which was accompanied by typicalapoptotic morphological changes.(3) Deguelin could inhibit RPMI-8226 cell invasion.(4)Deguelin could downregulate the expression of SRC-3 and its downstream transcriptionfactor NF-κB,which thus influenced the gelatinolytic activity of secreted MMP-2 and -9.
Conclusion:Deguelin exhibit its strong antitumor effects via the interruption of SRC-3.
引文
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36. Cheng JQ, Lindsley CW, Chen, GZ, et al. The Akt/PKB pathway: molecular target for cancer drug discovery. Oncogene, 2005, 24: 7482-7492.
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3．Ollis WD，Ramsay MVJ，Sutherland IO，et al．Constitution of gambogic acid．Tetrahedron 1965，21：1453-1470．
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10．Zhao Q，Yang Y，Yu J，et al．Posttranscriptional regulation of the telomerase hTERT by gambogic acid in human gastric carcinoma 823 cells．Cancer Letters，2008，262：223-231．
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13．Liu HL，Chen Y，Cui GH，et al．Deguelin regulates nuclear pore complex proteins Nup98 and Nup88 in U937 cells in vitro．Acta pharmacol sinica，2005，26： 1265-1273．
14．Chen WH，Chen Y，Cui GH，et al．Deguelin inhibits expression of I-κBα protein in Raji and U937 cells．Acta pharmacol sinica，2006，27： 485-490．
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29. Sakakura C, Hagiwara A, Yasuoka R, et al. Amplification and over-expression of the AIB1 nuclear receptor co-activator gene in primary gastric cancers. Int J Cancer, 2000,89: 217-223.
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31. Li H, Chen JD. The receptor-associated coactivator 3 activates transcription through CREB-binding protein recruitment and autoregulation. J Biol Chem, 1998, 273:5948-5954.
32. Colo GP, Rosato RR, Grant S, et al. RAC3 down-regulation sensitizes human chronic myeloid leukemia cells to TRAIL-induced apoptosis. FEBS Letters, 2007, 581:5075-5081.
33. Esteyries S, Perot C, Adelaide J, et al. NCOA3, a new fusion partner for MOZ/MYST3 in M5 acute myeloid leukemia. Leukemia, 2008, 22: 663-665.
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1．Autherhoff H，Frauendorf H，Liesenklas W，et al．Chemistry of gamboge．I．The chief constituent of gamboge resin．Archiv der Pharmazie，1962，295： 833-846．
2．Ollis WD，Ramsay MVJ，Sutherland IO，et al．Constitution of gambogic acid．Tetrahedron，1965，21：1453-1470．
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7．Wang Y，Chen Y，Chen Z，et al．Gambogic acid induces death inducer-obliterator 1-mediated apoptosis in Jurkat T cells．Acta Pharm Sin，2008，29： 349-354．
8．郭青龙，赵丽，吴照球等．藤黄酸对实验性动物造血．功能及免疫功能的影响．中国天然药物，2003，1： 229-232．
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10．Pandey MK，Sung B，Ahn KS，et al．Gambogic acid，a novel ligand for transferrin receptor，potentiates TNF-induced apoptosis through modulation of the nuclear factor-kB signaling pathway．Blood，2007，110： 3517-3525．
11．Zhao Q，Yang Y，Yu J，et al．Posttranscriptional regulation of the telomerase hTERT by gambogic acid in human gastric carcinoma 823 cells．Cancer Lett，2008，262：223-231．
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1．Udeani GO，Gerhauser C，Thomas CF，et al．Cancer chemopreventive activity mediated by deguelin，a naturally occurring rotenoid．Cancer Research，1997，57： 3424-3428．
2．Lee HY，Oh SH，Woo JK，et al．Chemopreventive effects of deguelin，a novel Akt inhibitor，on tobacco-induced lung tumorigenesis．J Natl Cancer Inst，2005，97：1695-1699．
3．Bortul R，Tazzari PL，Billi AM，et al．Deguelin，A PI3K/AKT inhibitor，enhances chemosensitivity of leukaemia cells with an active PI3K/AKT pathway．Br J Haematol，2005，129： 677-686．
4．Geeraerts B，Vanhoecke B，Vanden Berghe W，et al．Deguelin inhibits expression of IkappaB alpha protein and induces apoptosis of B-CLL cells in vitro．Leukemia，2007，21：1610-1618．
5．Chen WH，Chen Y，Cui GH．Deguelin inhibits expression of IkappaBalpha protein in Raji and U937 cells．Acta Pharmacol Sin，2006，27： 485-490．
6．Anzick SL，Kononen J，Walker RL，et al．AIB1，a steroid receptor coactivator amplified in breast and ovarian cancer．Science，1997，277： 965-968．
7. Liao L, Kuang SQ, Yuan Y, et al. Molecular structure and biological function of the cancer-amplified nuclear receptor coactivator SRC-3/AIB1. J Steroid Biochem Mol Biol, 2002, 83:3-14.
8. Suen CS, Berrodin TJ, Mastroeni R, et al. A transcriptional coactivator, steroid receptor coactivator-3, selectively augments steroid receptor transcriptional activity. J Biol Chem, 1998, 16:27645-27653.
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10. Ying H, Furuya F, Willingham MC, et al. Dual functions of the steroid hormone receptor coactivator 3 in modulating resistance to thyroid hormone. Mol Cell Biol,2005, 25: 7687-7695.
11. Werbajh S, Nojek I, Lanz R, et al. RAC-3 is a NF-kappa B coactivator. FEBS Lett, 2000,485: 195-199.
12. Yan J, Yu CT, Ozen M, et al. Steroid receptor coactivator-3 and activator protein-1 coordinately regulate the transcription of components of the insulin-like growth factor/AKT signaling pathway. Cancer Res, 2006, 66: 11039-11046.
13. Louie MC, Zou JX, Rabinovich A, et al. ACTR./AIB1 functions as an E2F1 coactivator to promote breast cancer cell proliferation and antiestrogen resistance. Mol Cell Biol,2004,24:5157-5171.
14. Weber AL, Rahemtullah A, Ferry JA. Hodgkin and non-Hodgkin lymphoma of the head and neck: clinical, pathologic, and imaging evaluation. Neuroimaging Clin N Am,2003, 13:371-392.
15. Gills JJ, Kosmeder J 2nd, Moon RC, et al. Effect of deguelin on UVB-induced skin carcinogenesis. J Chemother, 2005, 17: 297-301.
16. Jin Q, Feng L, Behrens C, et al. Implication of AMP-activated protein kinase and Akt-regulated survivin in lung cancer chemopreventive activities of deguelin. Cancer Res, 2007, 67: 11630-11639.
17. Liu HL, Chen Y, Cui GH, et al. Regulating expressions of cyclin D1, pRb, and anti-cancer effects of deguelin on human Burkitt's lymphoma Daudi cells in vitro. Acta Pharmacol sin, 2005, 26: 873-880.
18. Oh A, List HJ, Reiter R, et al. The nuclear receptor coactivator AIBl mediates insulin-like growth factor I-induced phenotypic changes in human breast cancer cells.Cancer Res, 2004, 64: 8299-8308.
19. Wu RC, Qin J, Hashimoto Y, et al, O'Malley BW. Regulation of SRC-3 (pCIP/ACTR/AIB-1/RAC-3/TRAM-1) coactivator activity by I kappa B kinase. MolCell Biol, 2002, 22: 3549-3561.
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22. Henke RT, Haddad BR, Kim SE, et al. Overexpression of the Nuclear Receptor Coactivator AIBl (SRC-3) during Progression of Pancreatic Adenocarcinoma. Clin Cancer Res, 2004, 10: 6134-6142.
23. Sakakura C, Hagiwara A, Yasuoka R, et al. Amplification and over-expression of the AIBl nuclear receptor co-activator gene in primary gastric cancers. Int J Cancer, 2000,89:217-223.
24. Wang Y, Wu MC, Sham JS, et al. Prognostic significance of c-myc and AIBl amplification in hepatocellular carcinoma. A broad survey using high-throughput tissue microarray. Cancer, 2002, 95: 2346-2352.
25. Li H, Chen JD. The receptor-associated coactivator 3 activates transcription through CREB-binding protein recruitment and autoregulation. J Biol Chem, 1998, 273: 5948-5954.
26. Colo GP, Rosato RR, Grant S, et al. RAC3 down-regulation sensitizes human chronic myeloid leukemia cells to TRAIL-induced apoptosis. FEBS Letters, 2007, 581:5075-5081.
27. Esteyries S, Perot C, Adelaide J, et al. NCOA3, a new fusion partner for MOZ/MYST3 in M5 acute myeloid leukemia. Leukemia, 2008, 22: 663-665.
28. Torres-Arzayus MI, De Mora JF, Yuan J, et al. High tumor incidence and activation of the PI3K/AKT pathway in transgenic mice define AIBl as an oncogene. Cancer Cell,2004, 6: 263-274.
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1．Zhou G，Hashimoto Y，Kwak I，et al．Role of the steroid receptor coactivator SRC-3 in cell growth．Mol Cell Biol，2003，23：7742-7755．
2．Udeani GO，Gerhauser C，Thomas CF，et al．Cancer chemopreventive activity mediated by deguelin，a naturally occurring rotenoid．Cancer Research，1997，57： 3424-3428.
3. Woo JK, Choi DS, Tran HT, et al. Liposomal encapsulation of deguelin: evidence for enhanced antitumor activity in tobacco carcinogen-induced and oncogenic K-ras-induced lung tumorigenesis. Cancer Prev Res (Phila Pa), 2009, 2: 361-369.
4. Lee JH, Lee DH, Lee HS, et al. Deguelin inhibits human hepatocellular carcinoma by antiangiogenesis and apoptosis. Oncol Rep, 2008, 20: 129-134.
5. Murillo G, Salti GI, Kosmeder JW, et al. Deguelin inhibits the growth of colon cancer cells through the induction of apoptosis and cell cycle arrest. Eur J Cancer, 2002, 38:2446-2454.
6. Liu HL, Chen Y, Cui GH, et al. Experimental Study on Regulating Expressions of Cyclin Dl, pRb and Anticancer Effects of Deguelin on Human Burkitt's Lymphoma Daudi cells in vitro. Acta Pharmacol Sin, 26: 873-880.
7. Shu W, Chen Y, Wu Q, et al. Deguelin represses both the expression of nucleophosmin and some nucleoporins: Nup88 and Nup214 in Jurkat cells. Biol Pharm Bull, 2008, 31:27-32.
8. Lee HY. Molecular mechanisms of deguelin-induced apoptosis in transformed human bronchial epithelial cells. Biochem Pharmacol, 2004, 68: 1119-1124.
9. Gills JJ, Kosmeder J, Moon RC, et al. Effect of deguelin on UVB-induced skin carcinogenesis. J Chemother, 2005, 17: 297-301.
10. Jin Q, Feng L, Behrens C, et al. Implication of AMP-activated protein kinase and Akt-regulated survivin in lung cancer chemopreventive activities of deguelin. CancerRes, 2007, 67: 11630-11639.
11. Lee HY, Oh SH, Woo JK, et al. Chemopreventive effects of deguelin, a novel Akt inhibitor, on tobacco-induced lung tumorigenesis. J Natl Cancer Inst, 2005, 97: 1695-1669.
12. Chen WH, Chen Y, Cui GH. Deguelin inhibits expression of IkappaBalpha protein in Raji and U937 cells. Acta Pharmacol Sin, 2006, 27: 485-490.
13. Oh A, List HJ, Reiter R, et al. The nuclear receptor coactivator AIBl mediates insulin-like growth factor Ⅰ-induced phenotypic changes in human breast cancer cells.Cancer Res, 2004, 64: 8299-8308.
14. Wu RC, Qin J, Hashimoto Y, et al. Regulation of SRC-3 (pCIP/ACTR/AIB-1/RAC-3/TRAM-1) coactivator activity by I kappa B kinase. Mol Cell Biol, 2002, 22:3549-3561.
15. Yan J, Tsai SY, Tsai MJ. SRC-3/AIB1: transcriptional coactivator in oncogenesis. Acta Pharmacologica Sinica, 2006, 27: 387-394.
16. Henke RT, Haddad BR, Kim SE, et al. Overexpression of the Nuclear Receptor Coactivator AIBl (SRC-3) during Progression of Pancreatic Adenocarcinoma. Clin Cancer Res, 2004, 10: 6134-6142.
17. Sakakura C, Hagiwara A, Yasuoka R, et al. Amplification and over-expression of the AIB1 nuclear receptor co-activator gene in primary gastric cancers. Int J Cancer, 2000,89:217-223.
18. Wang Y, Wu MC, Sham JS, et al. Prognostic significance of c-myc and AIBl amplification in hepatocellular carcinoma. A broad survey using high-throughput tissue microarray. Cancer, 2002, 95: 2346-2352.
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