姜黄素抗胰腺癌的作用机制

俞泽元; 王科深; 任彦先; 罗长江; 曹宏泰; 焦作义

doi:10.3969/j.issn.1001-5256.2018.04.044

姜黄素抗胰腺癌的作用机制

DOI: 10.3969/j.issn.1001-5256.2018.04.044

兰州大学第二医院普外一科

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中图分类号: R735.9
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出版历程
- 出版日期: 2018-04-20

Mechanism of action of curcumin in treatment of pancreatic cancer

First Department of General Surgery, Lanzhou University Second Hospital

摘要

摘要: 姜黄素是一种从姜科植物的根茎姜黄中提取的植物多酚,具有抗炎、抗氧化、抗肿瘤、增强放化疗敏感性及保护肝肾功能等多种药理作用。它参与调控胰腺癌发展过程中的多条相关信号通路及癌基因表达,可能成为潜在的抗胰腺癌药物。针对姜黄素抑制胰腺癌细胞的增殖、诱导凋亡,以及抑制胰腺癌细胞信号传导的机制作一综述。
- 胰腺肿瘤 /
- 姜黄素 /
- 药理作用分子作用机制 /
- 综述
Abstract: Curcumin is a polyphenol extracted from the rhizome of Rhizoma Curcumae Longae with anti-inflammatory, antioxidant, and antitumor effects.It can also increase the sensitivity to chemoradiotherapy and protect hepatic and renal function.It is involved in the regulation of various signaling pathways and the expression of oncogenes and thus may become a potential anti-tumor drug for pancreatic cancer.This article reviews the mechanism of action of curcumin in inhibiting the proliferation and inducing the apoptosis of pancreatic cancer cells and inhibiting the signaling pathways involved in pancreatic cancer.
- pancreatic neoplasms /
- curcumin /
- molecular mechanisms of pharmacological action /
- review

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参考文献(49)

[1]GUPTA SC, KISMALI G, AGGARWAL BB.Curcumin, a component of turmeric:from farm to pharmacy[J].Biofactors, 2013, 39 (1) :2-13.

[2]BASNET P, SKALKO-BASNET N.Curcumin:an anti-inflammatory molecule from a curry spice on the path to cancer treatment[J].Molecules, 2011, 16 (6) :4567-4598.

[3]REUTER S, EIFES S, DICATO M, et al.Modulation of anti-apoptotic and survival pathways by curcumin as a strategy to induce apoptosis in cancer cells[J].Biochem Pharmacol, 2008, 76 (11) :1340-1351.

[4]PARK W, AMIN AR, CHEN ZG, et al.New perspectives of curcumin in cancer prevention[J].Cancer Prev Res, 2013, 6 (5) :387-400.

[5]GOEL A, AGGARWAL BB.Curcumin, the golden spice from indian saffron, is a chemosensitizer and radiosensitizer for tumors and chemoprotector and radioprotector for normal organs[J].Nutr Cancer, 2010, 62 (7) :919-930.

[6]JACOB JN, BADYAL DK, BALA S, et al.Evaluation of the in vivo anti-inflammatory and analgesic and in vitro anti-cancer activities of curcumin and its derivatives[J].Nat Prod Commun, 2013, 8 (3) :359-362.

[7]BIMONTE S, BARBIERI A, PALMA G, et al.Curcumin inhibits tumor growth and angiogenesis in an orthotopic mouse model of human pancreatic cancer[J].Biomed Res Int, 2013, 2013:810423.

[8]KWON YK, JUN JM, SHIN SW, et al.Curcumin decreases cell proliferation rates through BTG2-mediated cyclin D1 down-regulation in U937 cells[J].Int J Oncol, 2005, 26 (6) :1597-1603.

[9]AGGARWAL BB, BANERJEE S, BHARADWAJ U, et al.Curcumin induces the degradation of cyclin E expression through ubiquitin-dependent pathway and up-regulates cyclin-dependent kinase inhibitors p21 and p27 in multiple human tumor cell lines[J].Biochem Pharmacol, 2007, 73 (7) :1024-1032.

[10]JANSON V, JOHANSSON A, GRANKVIST K.Resistance to caspase-8 and-9 fragments in a malignant pleural mesothelioma cell line with acquired cisplatin-resistance[J].Cell Death Dis, 2010, 1:e78.

[11]PU J, LI X, ZHU J, et al.Expression and roles of poly (ADP-ribose) polymerase-1 and caspase-3 in pancreatic cancer and adjacen[J].J Clin Hepatol, 2016, 32 (2) :337-341. (in Chinese) 蒲竞, 李汛, 朱骏, 等.PARP-1和caspase-3在胰腺癌及癌旁组织中的表达及意义[J].临床肝胆病杂志, 2016, 32 (2) :337-341.

[12]GUPTA SC, PATCHVA S, KOH W, et al.Discovery of curcumin, a component of golden spice, and its miraculous biological activities[J].Clin Exp Pharmacol Physiol, 2012, 39 (3) :283-299

[13]HATCHER H, PLANALP R, CHO J, et al.Curcumin:from ancient medicine to current clinical trials[J].Cell Mol Life Sci, 2008, 65 (11) :1631-1652.

[14] REUTER S, EIFES SM, AGGARWAL B, et al.Modulation of anti-apoptotic and survival pathways by curcumin as a strategy to induce apoptosis in cancer cells[J].Biochem Pharmacol, 2008, 76 (76) :1340-1351.

[15] GLIENKE W, MAUTE L, WICHT J, et al.Curcumin inhibits constitutive STAT3 phosphorylation in human pancreatic cancer cell lines and downregulation of survivin/BIRC5 gene expression[J].Cancer Invest, 2010, 28 (2) :166-171.

[16]JUTOORU I, CHADALAPAKA G, LEI P, et al.Inhibition of NFκB and pancreatic cancer cell and tumor growth by curcumin is dependent on specificity protein down-regulation[J].J Biol Chem, 2010, 285 (33) :25332-25344.

[17]JUTOORU I, CHADALAPAKA G, LEI P, et al.Inhibition of NFkappa B and pancreatic cancer cell and tumor growth by curcumin is dependent on specificity protein down-regulation[J].J Biol Chem, 2010, 285 (285) :25332-25344.

[18]WILKEN R, VEENA MS, WANG MB, et al.Curcumin:a review of anti-cancer properties and therapeutic activity in head and neck squamous cell carcinoma[J].Mol Cancer, 2011, 10:12.

[19]ABEL EV, KIM EJ, WU J, et al.The Notch pathway is important in maintaining the cancer stem cell population in pancreatic cancer[J].PLo S One, 2014, 9 (3) :e91983.

[20]DU X, WANG YH, WANG ZQ, et al.Down-regulation of Notch1by small interfering RNA enhances chemosensitivity to gemcitabine in pancreatic cancer cells through activating apoptosis activity[J].J Zhejiang Univ:Med Sci, 2014, 43 (3) :313-318. (in Chinese) 杜潇, 王从涵, 王自强, 等.小分子干扰RNA沉默Notch1后增加胰腺癌细胞凋亡活性而提高吉西他滨化疗敏感性[J].浙江大学学报:医学版, 2014, 43 (3) :313-318.

[21]SUBRAMANIAM D, NICHOLES N, MAY R, et al.Abstract5046:SR1264, a novel tetrafluoro analog of curcumin prevents pancreatic tumor growth in vivo by suppressing Notch signaling pathway[J].Cancer Res, 2011, 70 (8 Suppl) :5046.

[22]LI H, HUANG C, HUANG K, et al.STAT3 knockdown reduces pancreatic cancer cell invasiveness and matrix metalloproteinase-7expression in nude mice[J].PLo S One, 2011, 6 (10) :e25941.

[23]GLIENKE W, MAUTE L, WICHT J, et al.Curcumin inhibits constitutive STAT3 phosphorylation in human pancreatic cancer cell lines and downregulation of survivin/BIRC5 gene expression[J].Cancer Invest, 2010, 28 (2) :166-171.

[24]YAO Q, LIN M, WANG Y, et al.Curcumin induces the apoptosis of A549 cells via oxidative stress and MAPK signaling pathways[J].Int J Mol Med, 2015, 36 (4) :1118-1126.

[25]JING L, XIANG ST, ZHANG QH, et al.Combination of curcumin and bicalutamide enhanced the growth inhibition of androgen-independent prostate cancer cells through SAPK/JNK and MEK/ERK1/2-mediated targeting NF-κB/p65 and MUC1-C[J].J Exp Clin Canc Res, 2015, 34 (1) :1-11.

[26]THAKKAR A, SUTARIA D, GRANDHI K, et al.Abstract A65:activation of ERK1/2 using combination of aspirin, curcumin and sulforaphane regimen leads to NF-B inhibition and apoptosis in pancreatic cancer cells[J].Cancer Prev Res, 2014, 5 (11 Suppl) :a65.

[27]LEV-ARI S, STARR A, VEXLER A, et al.Inhibition of pancreatic and lung adenocarcinoma cell survival by curcumin is associated with increased apoptosis, down-regulation of COX-2 and EGFR and inhibition of Erk1/2 activity[J].Anticancer Res, 2006, 26 (6B) :4423-4430.

[28]ZHANG Y, ZHOU YF, HU M.Research progress of traditional Chinese medicine for the invasion and metastasis of hepatocellular carcinoma[J].Chin J Clin pharmacol Ther, 2017, 22 (5) :594-600. (in Chinese) 张颖, 周缓凤, 胡敏.肝癌侵袭转移的中医药研究进展[J].中国临床药理学与治疗学, 2017, 22 (5) :594-600.

[29]ROY SK, SRIVASTAVA RK, SHANKAR S.Inhibition of PI3K/AKT and MAPK/ERK pathways causes activation of FOXO transcription factor, leading to cell cycle arrest and apoptosis in pancreatic cancer[J].J Mol Signal, 2010, 5:10.

[30]ZHAO Z, LI C, XI H, et al.Curcumin induces apoptosis in pancreatic cancer cells through the induction of forkhead box O1 and inhibition of the PI3K/Akt pathway[J].Mol Med Rep, 2015, 12 (4) :5415-5422.

[31]JONSON T, ALBRECHTSSON E, AXELSON J, et al.Altered expression of TGFB receptors and mitogenic effects of TGFB in pancreatic carcinomas[J].Int J Oncol, 2001, 19 (1) :71-81.

[32]OSHIMA M, OKANO K, MURAKI S, et al.Immunohistochemically detected expression of 3 major genes (CDKN2A/p16, TP53, and SMAD4/DPC4) strongly predicts survival in patients with resectable pancreatic cancer[J].Ann Surg, 2013, 258 (2) :336-346.

[33]GU ZY, LI SY, XIAO ZW, et al.The anti-tumor effect and mechanism of curcumin in pancreatic cancer[J].Tianjin Med J, 2014, 42 (12) :1159-1162. (in Chinese) 谷倬宇, 李思源, 肖智伟, 等.姜黄素的抗胰腺癌作用及相关机制研究[J].天津医药, 2014, 42 (12) :1159-1162.

[34]FRYER R, LABARTHE MC, DALGLEISH A, et al.The novel anti-cancer agent curcumin induces cytotoxicity in pancreatic cancer cell lines in vitro[J].Cancer Res, 2008, 68:5673-5673.

[35]MORRIS JP, WANG SC, HEBROK M.KRAS, Hedgehog, Wnt and the twisted developmental biology of pancreatic ductal adenocarcinoma[J].Nat Rev Cancer, 2010, 10 (10) :683-695.

[36]ZHANG Y, YAN W, SCHOFIELD HK, et al.Canonical wnt signaling is required for pancreatic carcinogenesis[J].Cancer Res, 2013, 73 (15) :4909-4922.

[37]AHN J, LEE H, KIM S, et al.Curcumin-induced suppression of adipogenic differentiation is accompanied by activation of Wnt/beta-catenin signaling[J].Am J Physiol Cell Physiol, 2010, 298 (6) :1510-1516.

[38]CHEN YC, ZHOU B, CHEN XM, et al.Effect of curcumin on the human colon cancer cells SW480[J].Chin J Clin Pharmacol Ther, 2017, 22 (5) :526-530. (in Chinese) 陈永财, 周斌, 陈雪敏, 等.姜黄素靶向抑制SW480细胞信号通路研究[J].中国临床药理学与治疗学, 2017, 22 (5) :526-530.

[39]LI SH, FU J, WATKINS DN, et al.Sulforaphane regulates selfrenewal of pancreatic cancer stem cells through the modulation of Sonichedgehog-GLI pathway[J].Mol Cell Biochem, 2013, 373 (1-2) :217-227.

[40]MAGLIANO MPD, HEBROK M.Hedgehog signaling pathways in pancreatic cancer pathogenesis[M].New York:Springer, 2010.

[41]SUN XD, LIU XE.Curcumin induces apoptosis of pancreatic cancer cells by inhibiting Ras-ERK and Shh-GLI1 signal pathways[J].Chin J Pathophysiol, 2012, 28 (6) :996-1000. (in Chinese) 孙晓东, 刘杏娥.姜黄素通过抑制Ras-ERK和Shh-GLI1信号诱导胰腺癌细胞凋亡[J].中国病理生理杂志, 2012, 28 (6) :996-1000.

[42]ELAMIN MH, SHINWARI Z, HENDRAYANI SF, et al.Curcumin inhibits the Sonic Hedgehog signaling pathway and triggers apoptosis in medulloblastoma cells[J].Mol Carcinog, 2010, 49 (3) :302-314.

[43]EL-AZAB M, HISHE H, MOUSTAFA Y, et al.Anti-angiogenic effect of resveratrol or curcuminin Ehrlichascites carcinomabearingmice[J].Eur J Pharmacol, 2011, 652 (1-3) :7-14.

[44]WEY JS, FAN FBS, GRAY MJ, et al.Vascular endothelial growth factor receptor-1 promotes migration and invasion in pancreatic carcinoma cell lines[J].Cancer, 2005, 104 (2) :427-438.

[45]SYLVESTER J, LIACINI A, WEN QL, et al.Interleukin-17 signal transduction pathways implicated in inducing matrix metalloproteinase-3, -13 and aggrecanase-1 genes in articular chondrocytes[J].Cell Signal, 2004, 16 (4) :469-476.

[46]ALI S, AHMAD AS, PADHYE S, et al.Gemcitabine sensitivity can be induced in pancreatic cancer cells through modulation of miR-200 and miR-21 expression by curcumin or its analogue CDF[J].Cancer Research, 2010, 70 (9) :3606-3617.

[47]BAI MH, ZHANG Y, WANG BF, et al.Mechanism of curcuminenhanced radiosensitivity in pancreatic cancer cells PANC-1[J].Chin J Radiol Med Prot, 2013, 33 (4) :360-363. (in Chinese) 白明华, 张扬, 王宝峰, 等.姜黄素提高人胰腺癌PANC-1细胞放射敏感性的机制研究[J].中华放射医学与防护杂志, 2013, 33 (4) :360-363.

[48]GONG AX, GUAN FL, LIU M, et al.Effects of curcumin combined with nimesulide on pancreatic cancer cells[J].Chin J Dig, 2005, 25 (1) :48-49. (in Chinese) 宫爱霞, 关凤林, 刘敏, 等.姜黄素与尼美舒利联合应用对胰腺癌细胞的作用[J].中华消化杂志, 2005, 25 (1) :48-49.

[49]KURIEN BT, SCOFIELD RH.Oral administration of heat-solubilized curcumin for potentially increasing curcumin bioavailability in experimental animals[J].Int J Cancer, 2009, 125 (8) :1992-1993.

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