维生素E琥珀酸酯诱导乳腺癌细胞凋亡机制的研究进展
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摘要
维生素E琥珀酸酯(vitamin E succinate,VES)是天然维生素E衍生物,具有抑制不同肿瘤细胞生长、增殖和选择性诱导肿瘤细胞凋亡的作用。VES能够有效的抑制乳腺癌细胞增殖作用,其作用机制主要与Fas蛋白及TGF-β1蛋白水平上调有关。VES联合化疗药物后能够使乳腺癌细胞表面的Fas表达上调,显著的抑制细胞增殖,诱导细胞凋亡。VES与他莫西酚(Tamoxifen,TAM)具有协同作用,联合用药后对乳腺癌细胞的凋亡诱导作用增强。因此,这些机制的研究发现可以评价VES的临床应用价值,对肿瘤学的发展及抗肿瘤药物的开发起着重要作用。
A vitamin E derivative,vitamin E succinate has the effect of inhibiting the growth,proliferation and selective induction of tumor cell apoptosis. VES can effectively inhibit the proliferation of breast cancer cells,and its mechanism is mainly related to Fas protein and TGF-β1 protein level. The higher Fas or TGF-β1 expression,cell apoptosis is higher. The Fas expression on the surface of breast cancer cells was up-regulated after VES combined with chemotherapy drugs,which significantly inhibited cell proliferation and induced apoptosis. VES and Tamoxifen had synergistic effect,and the effect of apoptosis on breast cancer cells was enhanced after combination of drugs. Therefore,the findings of these mechanisms can evaluate the clinical application value of VES,promote the development of oncology,and develop safe and effective anti-tumor drugs.
A vitamin E derivative,vitamin E succinate has the effect of inhibiting the growth,proliferation and selective induction of tumor cell apoptosis. VES can effectively inhibit the proliferation of breast cancer cells,and its mechanism is mainly related to Fas protein and TGF-β1 protein level. The higher Fas or TGF-β1 expression,cell apoptosis is higher. The Fas expression on the surface of breast cancer cells was up-regulated after VES combined with chemotherapy drugs,which significantly inhibited cell proliferation and induced apoptosis. VES and Tamoxifen had synergistic effect,and the effect of apoptosis on breast cancer cells was enhanced after combination of drugs. Therefore,the findings of these mechanisms can evaluate the clinical application value of VES,promote the development of oncology,and develop safe and effective anti-tumor drugs.
引文
[1]Zhang D,Qiao JJ,Li M,et al.Breast cancer brain metastases:Clinical characteristics and prognosis[J].Modern Oncology,2017,25(7):1073-1077.[张冬,乔京京,李曼,等.乳腺癌脑转移预后风险分析[J].现代肿瘤医学,2017,25(7):1073-1077.]
[2]Gil Gil MJ,Martinez-Garcia M,Sierra A,et al.Breast cancerbrain metastases:A review of the literature and a current multidisciplinary management guideline[J].Clinical and Translational Oncology,2014,16(5):436-446.
[3]Zhao Y,Dong XQ,Li RG,et al.Evaluation of the pathological response and prognosis following neoadjuvant chemotherapy in molecular subtypes of breast cancer[J].Onco Targets Ther,2015,8:1511-1521.
[4]Huang X,Zhang Z,Jia L,et al.Endoplasmic reticulum stress contributes to vitamin E succinate-induced apoptosis in human gastric cancer SGC-7901 cells[J].Cancer Lett,2010,288(1):123-131.
[5]Liu Y,Liu WC,Tao YR.The relation between overexpression of Her2 and the therapy of breast cancer[J].Modern Oncology,2010,18(1):182-184.[刘尧,刘文超,陶玉荣.Her2过表达与乳腺癌治疗的相关性研究进展[J].现代肿瘤医学,2010,18(1):182-184.]
[6]Tian Y,Lv G,Yang Y,et al.Effects of vitamin D on renal fibrosis in diabetic nephropathy model rats[J].Int J Clin Exp Pathol,2014,7(6):3028-3037.
[7]Jordan M,Nayel A,Brownlow B,et al.Development and evaluation of tocopherol-rich argan oil-based nanoemulsions as vehicles possessing anticancer activity[J].Journal of Biomedical Nanotechnology,2012,8(6):944-956.
[8]Li Y,Hahn T,Garrison K,et al.The vitamin E analogueα-TEA stimulates tumor autophagy and enhances antigen cross-presentation[J].Cancer research,2012,72(14):3535-3545.
[9]Rodríguez-Enríquez S,Hernández-Esquivel L,Marín-Hernández A,et al.Molecular mechanism for the selective impairment of cancer mitochondrial function by a mitochondrially targeted vitamin E analogue[J].Biochimica et Biophysica Acta(BBA)-Bioenergetics,2012,1817(9):1597-1607.
[10]Constantinou C,Papas A,Constantinou AI.Vitamin E and cancer:Anonsight into the anticancer activities of vitamin E isomers and analogs[J].Int J Cancer,2008,123(4):739-752.
[11]Dalton S.Linking the cell cycle to cell fate decisions[J].Trends Cell Biol,2015,25(10):592-600.
[12]Cardenas E,Ghosh R.Vitamin E:A dark horse at the crossroad of cancer management[J].Biochem Pharmacol,2013,86(7):845-852.
[13]He XW,Xu L.Advances on the role of cell cycle related genes CDKN2A,TP53,RB1 and BRCA2 in malignancies[J].Modern Oncology,2018,26(1):153-158.[贺小威,徐玲.细胞周期相关基因CDKN2A、TP53、RB1和BRCA2在恶性肿瘤中的研究进展[J].现代肿瘤医学,2018,26(1):153-158.]
[14]William LS,Sharon EC,Koyamangalath K.The role of vitamin E in prostate cancer[J].Oxidative Stress in Cancer Biology and Therapy,2011,21:333-354.
[15]Kruspig B,Zhivotovsky B,Gogvadze V.Contrasting effects ofα-tocopheryl succinate on cisplatin-and etoposide-induced apoptosis[J].Mitochondrion,2013,13(5):533-538.
[16]Patacsil D,Osayi S,Tran AT,et al.Vitamin E succinate inhibits survivin and induces apoptosis in pancreatic cancer cells[J].Genes&Nutrition,2012,7(1):83-89.
[17]Nerlich AG,Bachmeier BE.Density-dependent lineage instability of MDA-MB-435 breast cancer cells[J].Oncology Letters,2013,5(4):1370-1374.
[18]Cheng G,Zielonka J,Mc Allister DM,et al.Mitochondria-targeted vitamin E analogs inhibit breast cancer cell energy metabolism and promote cell death[J].BMC Cancer,2013,13:285.
[19]Yao DF,Li JE.Research progress about the mechanisms of vitamin E succinate induced apoptosis of cancer cells[J].Journal of Guangxi Academy of Sciences,2010,26(2):146-149.[姚东方,李杰恩.维生素E琥珀酸酯诱导肿瘤细胞凋亡作用机制的研究进展[J].广西科学院学报,2010,26(2):146-149.]
[20]Zhang X,Peng X,Yu W,et al.Alpha-tocopheryl succinate enhances doxorubicin-induced apoptosis in human gastric cancer cells via promotion of doxorubicin influx and suppression of doxorubicin efflux[J].Cancer Letters,2011,307(2):174-181.
[21]Zhao Y,Hu JY,Li RG,et al.Enhanced NK cell adoptive antitumor effects against breast cancer in vitro via blockade of the TGF-βsignaling pathway[J].Onco Targets and Therapy,2015,8:1553-1559.
[22]Yu AL,Moriniere J,Welge-Lussen U.Vitamin E reduces TGFbeta2-induced changes in human trabecular meshwork cells[J].Current Eye Research,2013,38(9):952-958.
[23]Shun MC,Yu W,Gapor A,et al.Pro-apoptotic mechanisms of action of a novel vitamin E analog(α-TEA)and a naturally occurring form of vitamin E(δ-tocotrienol)in MDA-MB-435human breast cancer cells[J].Nutrition and Cancer,2004,48(1):95-105.
[24]Cheng G,Zielonka J,Dranka BP,et al.Mitochondria-targeted drugs synergize with 2-deoxyglucose to trigger breast cancer cell death[J].Cancer Research,2012,72(10):2634-2644.
[25]Sun JH,Li Y.The research progress of Fas/Fas L system in tumor cell apoptosis[J].Medical Recapitulate,2015,20(21):3694-3696.[孙建华,李雁.Fas/Fas L系统在肿瘤细胞凋亡中的研究进展[J].医学综述,2015,20(21),3694-3696.]
[26]Chi J,Teng M,Yu Z,et al.Marek's disease virus-encoded analog of micro RNA-155 activates the oncogene c-Myc by targeting LTBP1 and suppressing the TGF-βsignaling pathway[J].Virology,2014,476:72-84.
[27]Sun J,Liu YJ,Li SS,et al.Expression and clinical significance of Fas/Fas L and IL-10 in breast cancer tissues[J].Modern Oncology,2012,20(05):948-952.[孙建娜,刘运江,李胜水,等.Fas/Fas L系统和IL-10在乳腺癌组织中的表达及临床意义[J].现代肿瘤医学,2012,20(05):948-952.]
[28]Wu J.Clinicopathological study of Fas-related death domain protein expression in breast cancer[J].China Modern Medicine,2017,24(28):4-6.[吴嘉.Fas相关死亡结构域蛋白在乳腺癌中表达的临床病理研究[J].中国当代医药,2017,24(28):4-6.]
[29]Zhao Y,Hu JY,Li RG,et al.Construction of eukaryotic expression vector p TAR-GET-DNTβRⅡand its expression in breast cancer[J].Cancer Genetics and Epigenetics,2015,3(1):1-4.
[30]Lior HK,Li Y,Chen JS,et al.Targeting TGF-βsignaling in cancer[J].Expert Opinion on Therapeutic Targets,2013,17(7):743-760.
[31]Jiang QY,Li L,Chen XD,et al.Apoptosis of MDA-MB-453breast cancer cells with HER-2 overexpression induced by VES and its relationship with expression of Fas and TGF-β1[J].Chin J Cancer Prev Treat,2010,17(13):982-985.[姜秋颖,李里,陈旭东,等.VES诱导HER-2高表达乳腺癌细胞MDAMB-453凋亡及其与Fas及TGF-β1表达的相关性分析[J].中华肿瘤防治杂志,2010,17(13):982-985.]
[32]Yu W,Sanders BG,Kline K.RRR-a-tocopheryl succinateinduced apoptosis of humanbreast cancer cells involves Bax translocation to mitochondria[J].Cancer Research,2003,63(10):2483-2491.
[33]Kline K,Yu W,Sanders BG.Vitamin E:Mechanisms of action as tumor cell growth inhibitors[J].J Nutr,2001,131(1):161S-163S.
[34]Diao QX,Zhang JZ,Zhao T,et al.Vitamin E promotes breast cancer cell proliferation by reducing ROS production and p53 expression[J].Eur Rev Med Pharmacol Sci,2016,20(12):2710-2717.
[35]Yan B,Stantic M,Zobalova R,et al.Mitochondrially targeted vitamin E succinate efficiently kills breast tumour-initiating cells in a complexⅡ-dependent manner[J].BMC Cancer,2015,15:401.
[2]Gil Gil MJ,Martinez-Garcia M,Sierra A,et al.Breast cancerbrain metastases:A review of the literature and a current multidisciplinary management guideline[J].Clinical and Translational Oncology,2014,16(5):436-446.
[3]Zhao Y,Dong XQ,Li RG,et al.Evaluation of the pathological response and prognosis following neoadjuvant chemotherapy in molecular subtypes of breast cancer[J].Onco Targets Ther,2015,8:1511-1521.
[4]Huang X,Zhang Z,Jia L,et al.Endoplasmic reticulum stress contributes to vitamin E succinate-induced apoptosis in human gastric cancer SGC-7901 cells[J].Cancer Lett,2010,288(1):123-131.
[5]Liu Y,Liu WC,Tao YR.The relation between overexpression of Her2 and the therapy of breast cancer[J].Modern Oncology,2010,18(1):182-184.[刘尧,刘文超,陶玉荣.Her2过表达与乳腺癌治疗的相关性研究进展[J].现代肿瘤医学,2010,18(1):182-184.]
[6]Tian Y,Lv G,Yang Y,et al.Effects of vitamin D on renal fibrosis in diabetic nephropathy model rats[J].Int J Clin Exp Pathol,2014,7(6):3028-3037.
[7]Jordan M,Nayel A,Brownlow B,et al.Development and evaluation of tocopherol-rich argan oil-based nanoemulsions as vehicles possessing anticancer activity[J].Journal of Biomedical Nanotechnology,2012,8(6):944-956.
[8]Li Y,Hahn T,Garrison K,et al.The vitamin E analogueα-TEA stimulates tumor autophagy and enhances antigen cross-presentation[J].Cancer research,2012,72(14):3535-3545.
[9]Rodríguez-Enríquez S,Hernández-Esquivel L,Marín-Hernández A,et al.Molecular mechanism for the selective impairment of cancer mitochondrial function by a mitochondrially targeted vitamin E analogue[J].Biochimica et Biophysica Acta(BBA)-Bioenergetics,2012,1817(9):1597-1607.
[10]Constantinou C,Papas A,Constantinou AI.Vitamin E and cancer:Anonsight into the anticancer activities of vitamin E isomers and analogs[J].Int J Cancer,2008,123(4):739-752.
[11]Dalton S.Linking the cell cycle to cell fate decisions[J].Trends Cell Biol,2015,25(10):592-600.
[12]Cardenas E,Ghosh R.Vitamin E:A dark horse at the crossroad of cancer management[J].Biochem Pharmacol,2013,86(7):845-852.
[13]He XW,Xu L.Advances on the role of cell cycle related genes CDKN2A,TP53,RB1 and BRCA2 in malignancies[J].Modern Oncology,2018,26(1):153-158.[贺小威,徐玲.细胞周期相关基因CDKN2A、TP53、RB1和BRCA2在恶性肿瘤中的研究进展[J].现代肿瘤医学,2018,26(1):153-158.]
[14]William LS,Sharon EC,Koyamangalath K.The role of vitamin E in prostate cancer[J].Oxidative Stress in Cancer Biology and Therapy,2011,21:333-354.
[15]Kruspig B,Zhivotovsky B,Gogvadze V.Contrasting effects ofα-tocopheryl succinate on cisplatin-and etoposide-induced apoptosis[J].Mitochondrion,2013,13(5):533-538.
[16]Patacsil D,Osayi S,Tran AT,et al.Vitamin E succinate inhibits survivin and induces apoptosis in pancreatic cancer cells[J].Genes&Nutrition,2012,7(1):83-89.
[17]Nerlich AG,Bachmeier BE.Density-dependent lineage instability of MDA-MB-435 breast cancer cells[J].Oncology Letters,2013,5(4):1370-1374.
[18]Cheng G,Zielonka J,Mc Allister DM,et al.Mitochondria-targeted vitamin E analogs inhibit breast cancer cell energy metabolism and promote cell death[J].BMC Cancer,2013,13:285.
[19]Yao DF,Li JE.Research progress about the mechanisms of vitamin E succinate induced apoptosis of cancer cells[J].Journal of Guangxi Academy of Sciences,2010,26(2):146-149.[姚东方,李杰恩.维生素E琥珀酸酯诱导肿瘤细胞凋亡作用机制的研究进展[J].广西科学院学报,2010,26(2):146-149.]
[20]Zhang X,Peng X,Yu W,et al.Alpha-tocopheryl succinate enhances doxorubicin-induced apoptosis in human gastric cancer cells via promotion of doxorubicin influx and suppression of doxorubicin efflux[J].Cancer Letters,2011,307(2):174-181.
[21]Zhao Y,Hu JY,Li RG,et al.Enhanced NK cell adoptive antitumor effects against breast cancer in vitro via blockade of the TGF-βsignaling pathway[J].Onco Targets and Therapy,2015,8:1553-1559.
[22]Yu AL,Moriniere J,Welge-Lussen U.Vitamin E reduces TGFbeta2-induced changes in human trabecular meshwork cells[J].Current Eye Research,2013,38(9):952-958.
[23]Shun MC,Yu W,Gapor A,et al.Pro-apoptotic mechanisms of action of a novel vitamin E analog(α-TEA)and a naturally occurring form of vitamin E(δ-tocotrienol)in MDA-MB-435human breast cancer cells[J].Nutrition and Cancer,2004,48(1):95-105.
[24]Cheng G,Zielonka J,Dranka BP,et al.Mitochondria-targeted drugs synergize with 2-deoxyglucose to trigger breast cancer cell death[J].Cancer Research,2012,72(10):2634-2644.
[25]Sun JH,Li Y.The research progress of Fas/Fas L system in tumor cell apoptosis[J].Medical Recapitulate,2015,20(21):3694-3696.[孙建华,李雁.Fas/Fas L系统在肿瘤细胞凋亡中的研究进展[J].医学综述,2015,20(21),3694-3696.]
[26]Chi J,Teng M,Yu Z,et al.Marek's disease virus-encoded analog of micro RNA-155 activates the oncogene c-Myc by targeting LTBP1 and suppressing the TGF-βsignaling pathway[J].Virology,2014,476:72-84.
[27]Sun J,Liu YJ,Li SS,et al.Expression and clinical significance of Fas/Fas L and IL-10 in breast cancer tissues[J].Modern Oncology,2012,20(05):948-952.[孙建娜,刘运江,李胜水,等.Fas/Fas L系统和IL-10在乳腺癌组织中的表达及临床意义[J].现代肿瘤医学,2012,20(05):948-952.]
[28]Wu J.Clinicopathological study of Fas-related death domain protein expression in breast cancer[J].China Modern Medicine,2017,24(28):4-6.[吴嘉.Fas相关死亡结构域蛋白在乳腺癌中表达的临床病理研究[J].中国当代医药,2017,24(28):4-6.]
[29]Zhao Y,Hu JY,Li RG,et al.Construction of eukaryotic expression vector p TAR-GET-DNTβRⅡand its expression in breast cancer[J].Cancer Genetics and Epigenetics,2015,3(1):1-4.
[30]Lior HK,Li Y,Chen JS,et al.Targeting TGF-βsignaling in cancer[J].Expert Opinion on Therapeutic Targets,2013,17(7):743-760.
[31]Jiang QY,Li L,Chen XD,et al.Apoptosis of MDA-MB-453breast cancer cells with HER-2 overexpression induced by VES and its relationship with expression of Fas and TGF-β1[J].Chin J Cancer Prev Treat,2010,17(13):982-985.[姜秋颖,李里,陈旭东,等.VES诱导HER-2高表达乳腺癌细胞MDAMB-453凋亡及其与Fas及TGF-β1表达的相关性分析[J].中华肿瘤防治杂志,2010,17(13):982-985.]
[32]Yu W,Sanders BG,Kline K.RRR-a-tocopheryl succinateinduced apoptosis of humanbreast cancer cells involves Bax translocation to mitochondria[J].Cancer Research,2003,63(10):2483-2491.
[33]Kline K,Yu W,Sanders BG.Vitamin E:Mechanisms of action as tumor cell growth inhibitors[J].J Nutr,2001,131(1):161S-163S.
[34]Diao QX,Zhang JZ,Zhao T,et al.Vitamin E promotes breast cancer cell proliferation by reducing ROS production and p53 expression[J].Eur Rev Med Pharmacol Sci,2016,20(12):2710-2717.
[35]Yan B,Stantic M,Zobalova R,et al.Mitochondrially targeted vitamin E succinate efficiently kills breast tumour-initiating cells in a complexⅡ-dependent manner[J].BMC Cancer,2015,15:401.