木犀草素抗乳腺癌作用机制的研究进展
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摘要
木犀草素是一种广泛分布于自然植物中的黄酮化合物。研究显示木犀草素能抑制乳腺癌细胞增殖、转移、侵袭和血管生成,诱导乳腺癌细胞凋亡,是一种很有前景的抗乳腺癌药物。本文主要对近年来国内外有关木犀草素在体内外抗乳腺癌的作用机制进行综述。
Luteolin is a kind of flavonoid which is widely distributed in a variety of natural products.Luteolin can inhibit the proliferation,invasion,metastasis of the breast cancer cells,angiogenesis and induce apoptosis of the breast cancer cells,which is a very promising drug against breast cancer.This review summarized the advancement of molecular mechanism of antitumor activity of luteolin in vitro and vivo both at home and abroad.
Luteolin is a kind of flavonoid which is widely distributed in a variety of natural products.Luteolin can inhibit the proliferation,invasion,metastasis of the breast cancer cells,angiogenesis and induce apoptosis of the breast cancer cells,which is a very promising drug against breast cancer.This review summarized the advancement of molecular mechanism of antitumor activity of luteolin in vitro and vivo both at home and abroad.
引文
[1]Stewart B,Wild CP,World Cancer Report 2014[M].The International Agency for Research on Cancer,WHO,2014.
[2]Tu SH,Ho CT,Liu MF,et al.Luteolin sensitises drug-resistant human breast cancer cells to tamoxifen via the inhibition of cyclin E2 expression[J].Food Chem,2013,141(2):1553-1561.doi:10.1016/j.foodchem.2013.04.077.
[3]Wang W,Zhang L.Research Progress on antitumor effect of Luteolin[J].J Southeast Univ(Med Sci Edi),2014,33(2):218-221.[王伟,张犁.木犀草素抗肿瘤作用的研究进展[J].东南大学学报:医学版,2014,33(2):218-221.]doi:10.3969/j.issn.1671-6264.2014.02.026.
[4]Zhao CQ,Guo ZY.Research Progress on pharmacological activity of Luteolin[J].J Chengde Med Coll,2015,32(2):148-150.[赵长祺,郭志义.木犀草素的药理作用研究进展[J].承德医学院学报,2015,32(2):148-150.]
[5]Peng YF,Zou WT,Xu CL.Evaluation of Flavonoids from Flos chrysanthemion Cell Proliferation in Human Cancer Cells[J].Chin Pharm J,2010,45(19):1454-1459.[彭钰芳,邹文韬,许传莲.杭白菊中黄酮类化合物及其抑制人源肿瘤细胞增殖活性的研究[J].中国药学杂志,2010,45(19):1454-1459.]
[6]Attoub S,Hassan AH,Vanhoecke B,et al.Inhibition of cell survival,invasion,tumor growth and histone deacetylase activity by the dietary flavonoid luteolin in human epithelioid cancer cells[J].Eur J Pharmacol,2011,651(1-3):18-25.doi:10.1016/j.ejphar.2010.10.063.
[7]Wang LM,Xie KP,Huo HN,et al.Luteolin inhibits proliferation induced by IGF-1 pathway dependent ERαin human breast cancer MCF-7 cells[J].Asian Pac J Cancer Prev,2012,13(4):1431-1437.
[8]Kapoor S.Luteolin and its inhibitory effect on tumor growth in systemic malignancies[J].Exp Cell Res,2013,319(6):777-778.doi:10.1016/j.yexcr.2013.01.006.
[9]Lee EJ,Oh SY,Sung MK.Luteolin exerts anti-tumor activity through the suppression of epidermal growth factor receptor-mediated pathway in MDA-MB-231 ER-negative breast cancer cells[J].Food Chem Toxicol,2012,50(11):4136-4143.doi:10.1016/j.fct.2012.08.025.
[10]Sui JQ,Xie KP,Xie MJ.Inhibitory effect of luteolin on the proliferation of human breast cancer cell lines induced by epidermal growth factor[J].Sheng Li Xue Bao,2016,68(1):27-34.
[11]Wang YH,Li AF,Fu CL,et al.Study on the anti-tumor effect of luteolin[J].Lishizhen Med Mater Med Res,2016,27(7):1587-1589.[王月华,李爱峰,付崇罗,等.木犀草素抗肿瘤活性研究[J].时珍国医国药,2016,27(7):1587-1589.]
[12]Markaverich BM,Shoulars K,Rodriguez MA.Luteolin Regulation of Estrogen Signaling and Cell Cycle Pathway Genes in MCF-7 Human Breast Cancer Cells[J].Int J Biomed Sci,2011,7(2):101-111.
[13]Shi DD,Wang GM,Kuang YY,et al.Metabonomics Study on Luteolin Intervention of Breast Cancer MCF-7 Cells[J].Chin J Anal Chem,2014,42(8):1088-1093.[史栋栋,王桂明,况媛媛,等.细胞代谢组学用于木犀草素抑制MCF-7细胞的机制研究[J].分析化学,2014,42(8):1088-1093.]doi:10.11895/j.issn.0253-3820.131230.
[14]Shih YL,Liu HC,Chen CS,et al.Combination treatment with luteolin and quercetin enhances antiproliferative effects in nicotine-treated MDA-MB-231 cells by downregulating nicotinic acetylcholine receptors[J].J Agric Food Chem,2010,58(1):235-241.doi:10.1021/jf9031684.
[15]Rao PS,Satelli A,Moridani M,et al.Luteolin induces apoptosis in multidrug resistant cancer cells without affecting the drug transporter function:involvement of cell line-specific apoptotic mechanisms[J].Int J Cancer,2012,130(11):2703-2714.doi:10.1002/ijc.26308.
[16]Kim MJ,Woo JS,Kwon CH,et al.Luteolin induces apoptotic cell death through AIF nuclear translocation mediated by activation of ERK and p38 in human breast cancer cell lines[J].Cell Biol Int,2012,36(4):339-344.doi:10.1042/CBI20110394.
[17]Jiang Y,Xie KP,Huo HN,et al.Inhibitory effect of luteolin on the angiogenesis of chick chorioallantoic membrane and invasion of breast cancer via downregulation of AEG-1 and MMP-2[J].Acta Physiol Sin,2013,65(5):513-518.[姜英,谢鲲鹏,霍洪楠,等.木犀草素下调AEG-1和MMP-2的表达对血管生成和乳腺癌细胞侵袭性的抑制作用[J].生理学报,2013,65(5):513-518.]
[18]Wang LJ,Wang J.Luteolin induced apoptosis in breast cancer cell by decreasing the expression of micro RNA-21[J].Chongqing Med,2013,42(12):1374-1376.[王丽娟,王静.木犀草素抑制micro RNA-21的表达诱导乳腺癌细胞凋亡[J].重庆医学,2013,42(12):1374-1376.]doi:10.3969/j.issn.1671-8348.2013.12.021.
[19]Zhao L,Xiu YL,Chen S,et al.Expression of PTEN and AKT in Breast Cancer and Its Clinical Significance[J].China Cancer,2013,22(6):502-505.[赵林,修银铃,陈说,等.PTEN和AKT在乳腺癌中的表达及临床意义[J].中国肿瘤,2013,22(6):502-505.]doi:10.11735/j.issn.1004-0242.2013.06.2012331.
[20]Jeon YW,Suh YJ.Synergistic apoptotic effect of celecoxib and luteolin on breast cancer cells[J].Oncol Rep,2013,29(2):819-825.doi:10.3892/or.2012.2158.
[21]Yang MY,Wang CJ,Chen NF,et al.Luteolin enhances paclitaxel-induced apoptosis in human breast cancer MDAMB-231 cells by blocking STAT3[J].Chem Biol Interact,2014,213:60-68.doi:10.1016/j.cbi.2014.02.002.
[22]Cook MT,Liang Y,Besch-Williford C,et al.Luteolin inhibits progestin-dependent angiogenesis,stem cell-like characteristics,and growth of human breast cancer xenografts[J].Springerplus,2015,4:444.doi:10.1186/s40064-015-1242-x.
[23]Liu XF.Effect of luteolin on insulin like growth factor-1 in human breast cancer cells[J].Chin J Gerontol,2014,34(14):3967-3969.[刘雪飞.木犀草素对人乳腺癌细胞胰岛素样生长因子-1的影响[J].中国老年学杂志,2014,34(14):3967-3969.]doi:10.3969/j.issn.1005-9202.2014.14.074.
[24]Li WF,Ou Q,Zhang H,et al.Inhibition Effect of Luteolin on SDF-1α/CXCR4 Signal Pathway in Breast Cancer Cells MDA-MB-231[J].J Basic Clin Oncol,2014,27(3):199-202.[李文仿,欧琴,张华,等.木犀草素抑制乳腺癌细胞MDA-MB-231中SDF-1α/CXCR4通路的作用[J].肿瘤基础与临床,2014,27(3):199-202.]doi:10.3969/j.issn.1673-5412.2014.03.005.
[25]Wang H,Wang L.Study on antitumor and antimetastatic effect of luteolin[J].Chin J Hosp Pharm,2010,30(22):1915-1917.[王焕,王荔.木犀草素抗肿瘤转移作用[J].中国医院药学杂志,2010,30(22):1915-1917.]
[26]Caldon CE,Sergio CM,Kang J,et al.Cyclin E2 overexpression is associated with endocrine resistance but not insensitivity to CDK2 inhibition in human breast cancer cells[J].Mol Cancer Ther,2012,11(7):1488-1499.doi:10.1158/1535-7163.MCT-11-0963.
[2]Tu SH,Ho CT,Liu MF,et al.Luteolin sensitises drug-resistant human breast cancer cells to tamoxifen via the inhibition of cyclin E2 expression[J].Food Chem,2013,141(2):1553-1561.doi:10.1016/j.foodchem.2013.04.077.
[3]Wang W,Zhang L.Research Progress on antitumor effect of Luteolin[J].J Southeast Univ(Med Sci Edi),2014,33(2):218-221.[王伟,张犁.木犀草素抗肿瘤作用的研究进展[J].东南大学学报:医学版,2014,33(2):218-221.]doi:10.3969/j.issn.1671-6264.2014.02.026.
[4]Zhao CQ,Guo ZY.Research Progress on pharmacological activity of Luteolin[J].J Chengde Med Coll,2015,32(2):148-150.[赵长祺,郭志义.木犀草素的药理作用研究进展[J].承德医学院学报,2015,32(2):148-150.]
[5]Peng YF,Zou WT,Xu CL.Evaluation of Flavonoids from Flos chrysanthemion Cell Proliferation in Human Cancer Cells[J].Chin Pharm J,2010,45(19):1454-1459.[彭钰芳,邹文韬,许传莲.杭白菊中黄酮类化合物及其抑制人源肿瘤细胞增殖活性的研究[J].中国药学杂志,2010,45(19):1454-1459.]
[6]Attoub S,Hassan AH,Vanhoecke B,et al.Inhibition of cell survival,invasion,tumor growth and histone deacetylase activity by the dietary flavonoid luteolin in human epithelioid cancer cells[J].Eur J Pharmacol,2011,651(1-3):18-25.doi:10.1016/j.ejphar.2010.10.063.
[7]Wang LM,Xie KP,Huo HN,et al.Luteolin inhibits proliferation induced by IGF-1 pathway dependent ERαin human breast cancer MCF-7 cells[J].Asian Pac J Cancer Prev,2012,13(4):1431-1437.
[8]Kapoor S.Luteolin and its inhibitory effect on tumor growth in systemic malignancies[J].Exp Cell Res,2013,319(6):777-778.doi:10.1016/j.yexcr.2013.01.006.
[9]Lee EJ,Oh SY,Sung MK.Luteolin exerts anti-tumor activity through the suppression of epidermal growth factor receptor-mediated pathway in MDA-MB-231 ER-negative breast cancer cells[J].Food Chem Toxicol,2012,50(11):4136-4143.doi:10.1016/j.fct.2012.08.025.
[10]Sui JQ,Xie KP,Xie MJ.Inhibitory effect of luteolin on the proliferation of human breast cancer cell lines induced by epidermal growth factor[J].Sheng Li Xue Bao,2016,68(1):27-34.
[11]Wang YH,Li AF,Fu CL,et al.Study on the anti-tumor effect of luteolin[J].Lishizhen Med Mater Med Res,2016,27(7):1587-1589.[王月华,李爱峰,付崇罗,等.木犀草素抗肿瘤活性研究[J].时珍国医国药,2016,27(7):1587-1589.]
[12]Markaverich BM,Shoulars K,Rodriguez MA.Luteolin Regulation of Estrogen Signaling and Cell Cycle Pathway Genes in MCF-7 Human Breast Cancer Cells[J].Int J Biomed Sci,2011,7(2):101-111.
[13]Shi DD,Wang GM,Kuang YY,et al.Metabonomics Study on Luteolin Intervention of Breast Cancer MCF-7 Cells[J].Chin J Anal Chem,2014,42(8):1088-1093.[史栋栋,王桂明,况媛媛,等.细胞代谢组学用于木犀草素抑制MCF-7细胞的机制研究[J].分析化学,2014,42(8):1088-1093.]doi:10.11895/j.issn.0253-3820.131230.
[14]Shih YL,Liu HC,Chen CS,et al.Combination treatment with luteolin and quercetin enhances antiproliferative effects in nicotine-treated MDA-MB-231 cells by downregulating nicotinic acetylcholine receptors[J].J Agric Food Chem,2010,58(1):235-241.doi:10.1021/jf9031684.
[15]Rao PS,Satelli A,Moridani M,et al.Luteolin induces apoptosis in multidrug resistant cancer cells without affecting the drug transporter function:involvement of cell line-specific apoptotic mechanisms[J].Int J Cancer,2012,130(11):2703-2714.doi:10.1002/ijc.26308.
[16]Kim MJ,Woo JS,Kwon CH,et al.Luteolin induces apoptotic cell death through AIF nuclear translocation mediated by activation of ERK and p38 in human breast cancer cell lines[J].Cell Biol Int,2012,36(4):339-344.doi:10.1042/CBI20110394.
[17]Jiang Y,Xie KP,Huo HN,et al.Inhibitory effect of luteolin on the angiogenesis of chick chorioallantoic membrane and invasion of breast cancer via downregulation of AEG-1 and MMP-2[J].Acta Physiol Sin,2013,65(5):513-518.[姜英,谢鲲鹏,霍洪楠,等.木犀草素下调AEG-1和MMP-2的表达对血管生成和乳腺癌细胞侵袭性的抑制作用[J].生理学报,2013,65(5):513-518.]
[18]Wang LJ,Wang J.Luteolin induced apoptosis in breast cancer cell by decreasing the expression of micro RNA-21[J].Chongqing Med,2013,42(12):1374-1376.[王丽娟,王静.木犀草素抑制micro RNA-21的表达诱导乳腺癌细胞凋亡[J].重庆医学,2013,42(12):1374-1376.]doi:10.3969/j.issn.1671-8348.2013.12.021.
[19]Zhao L,Xiu YL,Chen S,et al.Expression of PTEN and AKT in Breast Cancer and Its Clinical Significance[J].China Cancer,2013,22(6):502-505.[赵林,修银铃,陈说,等.PTEN和AKT在乳腺癌中的表达及临床意义[J].中国肿瘤,2013,22(6):502-505.]doi:10.11735/j.issn.1004-0242.2013.06.2012331.
[20]Jeon YW,Suh YJ.Synergistic apoptotic effect of celecoxib and luteolin on breast cancer cells[J].Oncol Rep,2013,29(2):819-825.doi:10.3892/or.2012.2158.
[21]Yang MY,Wang CJ,Chen NF,et al.Luteolin enhances paclitaxel-induced apoptosis in human breast cancer MDAMB-231 cells by blocking STAT3[J].Chem Biol Interact,2014,213:60-68.doi:10.1016/j.cbi.2014.02.002.
[22]Cook MT,Liang Y,Besch-Williford C,et al.Luteolin inhibits progestin-dependent angiogenesis,stem cell-like characteristics,and growth of human breast cancer xenografts[J].Springerplus,2015,4:444.doi:10.1186/s40064-015-1242-x.
[23]Liu XF.Effect of luteolin on insulin like growth factor-1 in human breast cancer cells[J].Chin J Gerontol,2014,34(14):3967-3969.[刘雪飞.木犀草素对人乳腺癌细胞胰岛素样生长因子-1的影响[J].中国老年学杂志,2014,34(14):3967-3969.]doi:10.3969/j.issn.1005-9202.2014.14.074.
[24]Li WF,Ou Q,Zhang H,et al.Inhibition Effect of Luteolin on SDF-1α/CXCR4 Signal Pathway in Breast Cancer Cells MDA-MB-231[J].J Basic Clin Oncol,2014,27(3):199-202.[李文仿,欧琴,张华,等.木犀草素抑制乳腺癌细胞MDA-MB-231中SDF-1α/CXCR4通路的作用[J].肿瘤基础与临床,2014,27(3):199-202.]doi:10.3969/j.issn.1673-5412.2014.03.005.
[25]Wang H,Wang L.Study on antitumor and antimetastatic effect of luteolin[J].Chin J Hosp Pharm,2010,30(22):1915-1917.[王焕,王荔.木犀草素抗肿瘤转移作用[J].中国医院药学杂志,2010,30(22):1915-1917.]
[26]Caldon CE,Sergio CM,Kang J,et al.Cyclin E2 overexpression is associated with endocrine resistance but not insensitivity to CDK2 inhibition in human breast cancer cells[J].Mol Cancer Ther,2012,11(7):1488-1499.doi:10.1158/1535-7163.MCT-11-0963.