齐墩果酸抗肿瘤作用机制的研究进展
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摘要
恶性肿瘤已经成为严重威胁人类生命与健康的疾病之一,随着对恶性肿瘤治疗方面研究的不断进展,越来越多的抑制肿瘤的有效物质被发现。齐墩果酸(OA)是近年来发现的具有抑癌作用的重要植物提取物,多年来的研究表明其具有明显的抑制肿瘤生长的作用,随着对齐墩果酸研究的不断深入,其抗肿瘤作用的机制也逐渐被发现。研究结果表明齐墩果酸的抗肿瘤机制存在多条途径。
Malignant tumor has become one of the serious problems threatening human life and health.With the development of the research on malignant tumor treatment,more and more antitumor active substances have been found. Oleanolic acid( OA) is an important plant extract that can significantly inhibit the growth of cancer,which is found in recent years. With the deepening of research of OA,its anti-tumor mechanisms have also been identified,The results show that the anti-tumor mechanism of oleanolicacid in the presence of multiple way.
Malignant tumor has become one of the serious problems threatening human life and health.With the development of the research on malignant tumor treatment,more and more antitumor active substances have been found. Oleanolic acid( OA) is an important plant extract that can significantly inhibit the growth of cancer,which is found in recent years. With the deepening of research of OA,its anti-tumor mechanisms have also been identified,The results show that the anti-tumor mechanism of oleanolicacid in the presence of multiple way.
引文
[1]Yan SL,Huang CY,Wu ST,et al.Oleanolic acid and ursolic acid induce apoptosis in four human liver cancer cell lines[J].Toxicol In Vitro,2010,24(3):842-848.
[2]Rawendra RD,Lin PY,Chang CD,et al.Potentiation of Acute Promyelocytic Leukemia Cell Differentiation and Prevention of Leukemia Development in Mice by Oleanolic Acid[J].Anticancer Res,2015,35(12):6583-6590.
[3]Lúcio KA,Rocha Gda G,Mono-Ribeiro LC,et al.Oleanolic acid initiates apoptosis in non-small cell lung cancer cell lines and reduces metastasis of a B16F10 melanoma model in vivo[J].PLo S One,2011,6(12):e28596.
[4]李杰,许良中,朱伟萍,等.熊果酸与齐墩果酸体外抗Jurkat淋巴瘤细胞的研究[J].中国癌症杂志,1999,9(5):395-397.
[5]张鹏霞,李鸿梅,陈东,等.齐墩果酸诱导人白血病HL-60细胞凋亡及细胞周期阻滞[J].中国病理生理杂志,2008,24(10):1909-1911.
[6]Zhou R,Zhang Z,Zhao L,et al.Inhibition of m TOR signaling by oleanolic acid contributes to itsanti-tumor activity in osteosarcoma cells[J].J Orthop Res,2011,29(6):846-52
[7]黄开顺,朱链链,刘丹,等.齐墩果酸对肝癌细胞Hep3B增殖和凋亡的作用研究[J].第三军医大学学报,2011,33(5):531-534.
[8]Tan GT,Lee S,Lee IS,et al.Natural-product inhibitors of human DNA ligase I[J].Biochem J,1996,314:993-1000.
[9]李雯,王建华,徐世荣.有机酸诱导肿瘤细胞凋亡研究进展[J].现代肿瘤医学,2005,13(5):706-710.
[10]杨志明,王迪迪,李丽,等.Bcl-2参与SCID小鼠体内齐墩果酸诱导HL-60细胞凋亡的调控作用[J].吉林大学学报:医学版,2011,37(1):11-14.
[11]薛芳喜,葛堂栋,王迪迪,等.齐墩果酸对HL60细胞bc1-2和bax表达的影响[J].中国老年学杂志,2008,28(5):437-439.
[12]李鸿梅,王敬春,齐占朋,等.齐墩果酸对人早幼粒白血病NB4细胞增殖的影响及其机制[J].中国老年学杂志,2011,31(14):2702-2704.
[13]李鸿梅,李雪岩,蔡德富,等.齐墩果酸对顺铂耐药胃癌SGC-7901细胞增殖的影响及其机制研究[J].中国药理学通报,2009,25(10):1334-1337.
[14]张鹏霞,薛芳喜,王迪迪.齐墩果酸对K562细胞bax、bcl-x L mRNA表达的影响[J].中国老年学杂志,2009,29(21):2751-2752.
[15]Feng L,Au-Yeung W,Xu YH,et al.Oleanolic acid from Prunella Vulgaris L.induces SPC-A-1 cell line apoptosis via regulation of Bax,Bad and Bcl-2 expression[J].Asian Pac J Cancer Prev,2011,12(2):403-408.
[16]Shyu MH,Kao TC,Yen GC.Oleanolic acid and ursolic acid induce apoptosis in Hu H7 human hepatocellular carcinoma cells through a mitochondrial-dependentpathway and downregulation of XIAP[J].J Agric Food Chem,2010,58(10):6110-6118.
[17]Martín R,Carvalho-Tavares J,Ibeas E,et al.Acidic triterpenes compromise growth and survival of astrocytoma cell lines by regulating reactive oxygen species accumulation[J].Cancer Res,2007,67(8):3741-3751.
[18]吴珍,王启斌,陈永顺,等.齐墩果酸诱导人结肠癌Lo Vo细胞凋亡作用研究[J].医药导报,2011,30(2):176-180.
[19]Pratheeshkumar P,Kuttan G.Oleanolic acid induces apoptosis by modulatingp53,Bax,Bcl-2 and caspase-3 gene expression and regulates the activation oftranscription factors and cytokine profile in B16F[J].J Environ Pathol Toxicol Oncol,2011,30(1):21-31.
[20]Dubois C,Prevarskaya N,Vanden Abeele F.The calcium-signaling toolkit:Updates needed.Biochim Biophys Acta,2015.pii:S0167-4889(15)00417-6.
[21]卫小红,邵杰,王军辉,等.齐墩果酸诱导人肺腺癌细胞A549凋亡及其与细胞内钙离子的关系[J].同济大学学报:医学版,2009,30(5):19-23.
[22]黄敏珊,黄炜,吴其年,等.齐墩果酸诱导人乳腺癌细胞凋亡及与细胞内Ca2+水平关系的研究[J].中国现代医学杂志,2004,14(16):58-60.
[23]黄开顺,朱链链,刘丹,等.齐墩果酸抑制肝癌细胞QGY增殖和诱导凋亡的作用研究[J].世界科技研究与发展,2011,33(2):318-321.
[24]Dutta J,Fan Y,Gupta N,et al.Current insights into the regulation of programmed cell death by NF-kappa B[J].Oncogene,2006,25(51):6800-6816.
[25]苏剑东,吴灵飞.NF-κB与细胞凋亡[J].世界华人消化杂志,2007,15(12):1411-1416.
[26]Kucharczak J,Simmons MJ,Fan Y,et al.To be,or not to be:NF-kappa B is the answer--role of Rel/NF-kappa B in the regulation of apoptosis[J].Oncogene,2003,22(56):8961-8982.
[27]Bian X,Mc Allister-Lucas LM,Shao F,et al.NF-kappa B activation mediates doxorubicin-induced cell deathin N-type neuroblastoma cells[J].J Biol Chem,2001,276(52):48921-48929.
[28]Campbell KJ,Rocha S,Perkins ND.Active repression of antiapoptotic geneexpression by Rel A(p65)NF-kappa B[J].Mol Cell,2004,13(6):853-865.
[29]Ivanov VN,Ronai Z.p38 protects human melanoma cells from UV-inducedapoptosis through down-regulation of NF-kappa B activity and Fas expression[J].Oncogene,2000,19(26):3003-3012.
[30]Choi CY,You HJ,Jeong HG.Nitric oxide and tumor necrosis factor-alphaproduction by oleanolic acid via nuclear factor-kappa B activation in macrophages[J].Biochem Biophys Res Commun,2001,288(1):49-55.
[31]郭静,蒲咏梅,张东才.钙离子信号与细胞凋亡[J].生物物理学报,2005,21(1):1-18.
[32]Harper J,Moses MA.Molecular regulation of tumor angiogenesis:mechanisms andtherapeutic implications[J].EXS,2006(96):223-268.
[33]汤华成,赵蕾,张鹏霞,等.齐墩果酸对K562细胞系VEGF表达影响的实验研究[J].中国老年学杂志,2007,27(24):2371-2373.
[34]Lin CC,Huang CY,Mong MC,et al.Antiangiogenic potential of three triterpenic acids in human liver cancer cells[J].J Agric Food Chem,2011,59(2):755-762.
[35]Khasigov PZ,Podobed OV,Gracheva TS,et al.Roleof matrix metalloproteinases and their inhibitors in tumor invasion andmetastasis[J].Biochemistry(Mosc),2003,68(7):711-717.
[36]Davidson B,Reich R,Risberg B,et al.The biological role and regulationof matrix metalloproteinases(MMP)in cancer[J].Arkh Patol,2002,64(3):47-53.
[37]Caterina JJ,Yamada S,Caterina NC,et al.Inactivating mutation of the mousetissue inhibitor of metalloproteinases-2(Timp-2)gene alters pro MMP-2 activation[J].J Biol Chem,2000,275(34):26416-26422.
[38]Seo DW,Li H,Guedez L,et al.TIMP-2 mediated inhibition of angiogenesis:an MMP-independent mechanism[J].Cell,2003,114(2):171-180.
[39]张东方,黄炜,黄济群,等.齐墩果酸抗人肺癌细胞增殖,侵袭和诱导细胞凋亡的研究[J].肿瘤防治研究,2003,30(3):180-183
[40]Zhao X,Liu M,Li D.Oleanolic acid suppresses the proliferation of lungcarcinoma cells by miR-122/Cyclin G1/MEF2D axis[J].Mol Cell Biochem,2015,400(1/2):1-7.
[41]Paik KJ,Jeon SS,Chung HY,et al.Induction ofdifferentiation of the cultured rat mammary epithelial cells by triterpene acids[J].Arch Pharm Res,1998,21(4):398-405.
[2]Rawendra RD,Lin PY,Chang CD,et al.Potentiation of Acute Promyelocytic Leukemia Cell Differentiation and Prevention of Leukemia Development in Mice by Oleanolic Acid[J].Anticancer Res,2015,35(12):6583-6590.
[3]Lúcio KA,Rocha Gda G,Mono-Ribeiro LC,et al.Oleanolic acid initiates apoptosis in non-small cell lung cancer cell lines and reduces metastasis of a B16F10 melanoma model in vivo[J].PLo S One,2011,6(12):e28596.
[4]李杰,许良中,朱伟萍,等.熊果酸与齐墩果酸体外抗Jurkat淋巴瘤细胞的研究[J].中国癌症杂志,1999,9(5):395-397.
[5]张鹏霞,李鸿梅,陈东,等.齐墩果酸诱导人白血病HL-60细胞凋亡及细胞周期阻滞[J].中国病理生理杂志,2008,24(10):1909-1911.
[6]Zhou R,Zhang Z,Zhao L,et al.Inhibition of m TOR signaling by oleanolic acid contributes to itsanti-tumor activity in osteosarcoma cells[J].J Orthop Res,2011,29(6):846-52
[7]黄开顺,朱链链,刘丹,等.齐墩果酸对肝癌细胞Hep3B增殖和凋亡的作用研究[J].第三军医大学学报,2011,33(5):531-534.
[8]Tan GT,Lee S,Lee IS,et al.Natural-product inhibitors of human DNA ligase I[J].Biochem J,1996,314:993-1000.
[9]李雯,王建华,徐世荣.有机酸诱导肿瘤细胞凋亡研究进展[J].现代肿瘤医学,2005,13(5):706-710.
[10]杨志明,王迪迪,李丽,等.Bcl-2参与SCID小鼠体内齐墩果酸诱导HL-60细胞凋亡的调控作用[J].吉林大学学报:医学版,2011,37(1):11-14.
[11]薛芳喜,葛堂栋,王迪迪,等.齐墩果酸对HL60细胞bc1-2和bax表达的影响[J].中国老年学杂志,2008,28(5):437-439.
[12]李鸿梅,王敬春,齐占朋,等.齐墩果酸对人早幼粒白血病NB4细胞增殖的影响及其机制[J].中国老年学杂志,2011,31(14):2702-2704.
[13]李鸿梅,李雪岩,蔡德富,等.齐墩果酸对顺铂耐药胃癌SGC-7901细胞增殖的影响及其机制研究[J].中国药理学通报,2009,25(10):1334-1337.
[14]张鹏霞,薛芳喜,王迪迪.齐墩果酸对K562细胞bax、bcl-x L mRNA表达的影响[J].中国老年学杂志,2009,29(21):2751-2752.
[15]Feng L,Au-Yeung W,Xu YH,et al.Oleanolic acid from Prunella Vulgaris L.induces SPC-A-1 cell line apoptosis via regulation of Bax,Bad and Bcl-2 expression[J].Asian Pac J Cancer Prev,2011,12(2):403-408.
[16]Shyu MH,Kao TC,Yen GC.Oleanolic acid and ursolic acid induce apoptosis in Hu H7 human hepatocellular carcinoma cells through a mitochondrial-dependentpathway and downregulation of XIAP[J].J Agric Food Chem,2010,58(10):6110-6118.
[17]Martín R,Carvalho-Tavares J,Ibeas E,et al.Acidic triterpenes compromise growth and survival of astrocytoma cell lines by regulating reactive oxygen species accumulation[J].Cancer Res,2007,67(8):3741-3751.
[18]吴珍,王启斌,陈永顺,等.齐墩果酸诱导人结肠癌Lo Vo细胞凋亡作用研究[J].医药导报,2011,30(2):176-180.
[19]Pratheeshkumar P,Kuttan G.Oleanolic acid induces apoptosis by modulatingp53,Bax,Bcl-2 and caspase-3 gene expression and regulates the activation oftranscription factors and cytokine profile in B16F[J].J Environ Pathol Toxicol Oncol,2011,30(1):21-31.
[20]Dubois C,Prevarskaya N,Vanden Abeele F.The calcium-signaling toolkit:Updates needed.Biochim Biophys Acta,2015.pii:S0167-4889(15)00417-6.
[21]卫小红,邵杰,王军辉,等.齐墩果酸诱导人肺腺癌细胞A549凋亡及其与细胞内钙离子的关系[J].同济大学学报:医学版,2009,30(5):19-23.
[22]黄敏珊,黄炜,吴其年,等.齐墩果酸诱导人乳腺癌细胞凋亡及与细胞内Ca2+水平关系的研究[J].中国现代医学杂志,2004,14(16):58-60.
[23]黄开顺,朱链链,刘丹,等.齐墩果酸抑制肝癌细胞QGY增殖和诱导凋亡的作用研究[J].世界科技研究与发展,2011,33(2):318-321.
[24]Dutta J,Fan Y,Gupta N,et al.Current insights into the regulation of programmed cell death by NF-kappa B[J].Oncogene,2006,25(51):6800-6816.
[25]苏剑东,吴灵飞.NF-κB与细胞凋亡[J].世界华人消化杂志,2007,15(12):1411-1416.
[26]Kucharczak J,Simmons MJ,Fan Y,et al.To be,or not to be:NF-kappa B is the answer--role of Rel/NF-kappa B in the regulation of apoptosis[J].Oncogene,2003,22(56):8961-8982.
[27]Bian X,Mc Allister-Lucas LM,Shao F,et al.NF-kappa B activation mediates doxorubicin-induced cell deathin N-type neuroblastoma cells[J].J Biol Chem,2001,276(52):48921-48929.
[28]Campbell KJ,Rocha S,Perkins ND.Active repression of antiapoptotic geneexpression by Rel A(p65)NF-kappa B[J].Mol Cell,2004,13(6):853-865.
[29]Ivanov VN,Ronai Z.p38 protects human melanoma cells from UV-inducedapoptosis through down-regulation of NF-kappa B activity and Fas expression[J].Oncogene,2000,19(26):3003-3012.
[30]Choi CY,You HJ,Jeong HG.Nitric oxide and tumor necrosis factor-alphaproduction by oleanolic acid via nuclear factor-kappa B activation in macrophages[J].Biochem Biophys Res Commun,2001,288(1):49-55.
[31]郭静,蒲咏梅,张东才.钙离子信号与细胞凋亡[J].生物物理学报,2005,21(1):1-18.
[32]Harper J,Moses MA.Molecular regulation of tumor angiogenesis:mechanisms andtherapeutic implications[J].EXS,2006(96):223-268.
[33]汤华成,赵蕾,张鹏霞,等.齐墩果酸对K562细胞系VEGF表达影响的实验研究[J].中国老年学杂志,2007,27(24):2371-2373.
[34]Lin CC,Huang CY,Mong MC,et al.Antiangiogenic potential of three triterpenic acids in human liver cancer cells[J].J Agric Food Chem,2011,59(2):755-762.
[35]Khasigov PZ,Podobed OV,Gracheva TS,et al.Roleof matrix metalloproteinases and their inhibitors in tumor invasion andmetastasis[J].Biochemistry(Mosc),2003,68(7):711-717.
[36]Davidson B,Reich R,Risberg B,et al.The biological role and regulationof matrix metalloproteinases(MMP)in cancer[J].Arkh Patol,2002,64(3):47-53.
[37]Caterina JJ,Yamada S,Caterina NC,et al.Inactivating mutation of the mousetissue inhibitor of metalloproteinases-2(Timp-2)gene alters pro MMP-2 activation[J].J Biol Chem,2000,275(34):26416-26422.
[38]Seo DW,Li H,Guedez L,et al.TIMP-2 mediated inhibition of angiogenesis:an MMP-independent mechanism[J].Cell,2003,114(2):171-180.
[39]张东方,黄炜,黄济群,等.齐墩果酸抗人肺癌细胞增殖,侵袭和诱导细胞凋亡的研究[J].肿瘤防治研究,2003,30(3):180-183
[40]Zhao X,Liu M,Li D.Oleanolic acid suppresses the proliferation of lungcarcinoma cells by miR-122/Cyclin G1/MEF2D axis[J].Mol Cell Biochem,2015,400(1/2):1-7.
[41]Paik KJ,Jeon SS,Chung HY,et al.Induction ofdifferentiation of the cultured rat mammary epithelial cells by triterpene acids[J].Arch Pharm Res,1998,21(4):398-405.