一种新型的阳离子型姜黄素纳米粒对肝细胞癌增殖的影响

中国生物工程杂志

2010, Vol. 30

Issue (12): 30-35

研究报告

一种新型的阳离子型姜黄素纳米粒对肝细胞癌增殖的影响

张阳德^1,2, 段菁华^1,2, 陈玉祥^1,2, 廖明媚^1,2, 黄伯云³, 赵劲风^1,2

1. 中南大学卫生部肝胆肠外科研究中心长沙 410078;
2. 中南大学卫生部纳米生物技术重点实验室长沙 410078;
3. 中南大学粉末冶金国家重点实验室长沙 410083

Antiproliferative Effect of a Novel Cationic Nanocurcumin on Human Hepatocellular Carcinoma of HepG2 Cells

ZHANG Yang-de^1,2, DUAN Jing-hua^1,2, CHEN Yu-xiang^1,2, LIAO Ming-mei^1,2, HUANG Bo-yun³, ZHAO Jin-feng^1,2

1. National Hepatobiliary and Enteric Surgery Research Center, Ministry of Public Health, Central South University, Changsha 410078, China;
2. National Key Laboratory of Nanobiological Technology, Ministry of Public Health, Central South University, Changsha 410078, China;
3. State Key Laboratory for Power Metallurgy, Central South University, Changsha 410083, China

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摘要：

姜黄药用的主要有效成分是姜黄素,曾被认为是理想的抗癌化学治疗药物之一,然而,姜黄素在水中的溶解度低,体内吸收少,生物利用度低,极大地限制了它的应用。采用乳化聚合的方法,成功地制备了粒径在250nm左右的表面带正电荷的聚氰基丙烯酸正丁酯包载的姜黄素纳米粒,该纳米姜黄素仍然保留了姜黄素本身的生物活性,可抑制人肝癌细胞株HepG2细胞的生长,阻滞细胞周期于G₂/M期,对HepG2细胞有抗增殖作用,能诱导细胞凋亡,下调在肿瘤血管生长中起重要作用的血管内皮生长因子和调控血管内皮生长因子的环氧合酶-2的表达。

关键词： 纳米姜黄素; HepG2细胞; 细胞周期; 凋亡; 血管生成

Abstract:

Curcumin, obtained from the rhizomes of Curcuma longa L., Zingiberaceae (turmeric), are the most widely used phytoconstituent in food industry and recently for its therapeutic activity. It has very wide spectrum of therapeutic use like in inflammation, psoriasis and various tumors. But its highly lipophilic nature and very poor bioavailability hampers its therapeutic usefulness. The synthesized cationic poly(butyl) cyanoacrylate (PBCA) nanoparticles are coated with chitosan encapsulated formulation of curcumin-nanocurcumin. The particle size and zeta potential of prepared nanocurcumin was about 250nm and + 37.3 mV. The TEM study revealed the spherical nature of the prepared nanoparticles along with confirmation of particle size. MTT was used to assay the biologic activities of nanocurcumin and its anti-proliferative effect. Human hepatocellular carcinoma (HepG2) cells were treated with different concentration of nanocurcumin, curcumin and empty PBCA nanoparticles for 24h. MTT test showed that nanocurcumin was cytotoxic to HepG2 cells, the number of the apoptosis cell line increased. The inhibitory effect of nanocurcumin on cell growth was in a dose-dependent manner. Cell apoptosis percentage was gradually increased along with nanocurmumin concentration rising. The apoptosis rate for 5, 10, 20, 30, 40 and 50μg/ml is about 13.65%, 33.11%, 43.45%, 67.93%, 77.79% and 91.5% respectively.It shows obvious statistical difference against normal HepG2 cells.While the empty PBCA nanoparticles exhibit a low cytotoxicity to HepG2 cells. The morphologic alteration of HepG2 cells after treatment of nanocurcumin was observed under fluorescent microscope. When treated with nanocurcumin for 4h or longer time at 30μg/ml, HepG2 cells turned to circle, fell down from wall, and proliferated slowly. According to flow cytometry, after treatment with nanocurcumin, HepG2 cells were observed to block cell cycle in G2／M phase. Nanocurcumin has been shown to inhibit angiogenic biomarkers, vascular endothelial growth factor (VEGF) and cyclooxygenase-2 (COX-2) expression. Nanocurcumin’s mechanisms of action on liver cancer cells mirror that of free curcumin. Therefore, this kind of nanocurcumin could be used as a candidate for hepatocellular carcinoma (HCC) in the future. Nanocurcumin also provides an opportunity to expand the clinical application of this efficient agent by enabling ready aqueous dispersion. Future studies utilizing nanocurcumin are warranted in pre-clinical in vivo models of cancer and other diseases.

Key words: Nanocurcumin HepG2 cells Cell cycle Apoptosis Angiogenesis

收稿日期: 2010-08-31 出版日期: 2010-12-25

ZTFLH:

Q819

基金资助:

国家"十五""863"计划(2005AA473254) 、国家"十一五""863"计划(2007AA021809)、2009年湖南省研究生科研创新项目(CX2009B052)资助项目

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引用本文:

张阳德, 段菁华, 陈玉祥, 廖明媚, 黄伯云, 赵劲风. 一种新型的阳离子型姜黄素纳米粒对肝细胞癌增殖的影响[J]. 中国生物工程杂志, 2010, 30(12): 30-35.

ZHANG Yang-de, DUAN Jing-hua, CHEN Yu-xiang, LIAO Ming-mei, HUANG Bo-yun, ZHAO Jin-feng. Antiproliferative Effect of a Novel Cationic Nanocurcumin on Human Hepatocellular Carcinoma of HepG2 Cells. China Biotechnology, 2010, 30(12): 30-35.

链接本文:

https://manu60.magtech.com.cn/biotech/CN/ 或 https://manu60.magtech.com.cn/biotech/CN/Y2010/V30/I12/30

[1]	Guo L Y, Cai X F, Lee J J, et al. Comparison of suppressive effects of demethoxycurcumin and bisdemethoxycurcumin on expressions of inflammatory mediators in vitro and in vivo. Archives of Pharmacal Research, 2008, 31(4): 490-496.
[2]	Kunnumakkara A B, Anand P, Aggarwal B B. Curcumin inhibits proliferation, invasion, angiogenesis and metastasis of different cancers through interaction with mltiple cell signaling proteins. Cancer Letters, 2008, 269(2): 199-225.
[3]	Anand P, Kunnumakkara A B, Newman R A, et al. Bioavailability of curcumin: problems and promises. Mol Pharm, 2007, 4(6): 807-818.
[4]	Couvreur P, Dubernet C, Puisieux F. Controlled drug delivery with nanoparticles: current possibilities and future trends. Eur J Pharm Biopharm, 1995, 41(1): 2-13.
[5]	Huang C Y, Chen C M, Lee Y D. Synthesis of high loading and encapsulation efficient paclitaxel-loaded poly(n-butyl cyanoacrylate) nanoparticles via miniemulsion. Int J Pharm, 2007, 338(1-2): 267-275.
[6]	Ambruosi A, Yamamoto H, Kreuter J. Body distribution of polysorbate-80 and doxorubicin-loaded poly(butyl cyanoacrylate) nanoparticles after i.v. administration in rats. J Drug Targeting, 2005, 13(10): 535-542.
[7]	Lescure F, Zimmer C, Roy D, et al. Optimization of polyalkylcyanoacrylate nanoparticle preparation: influence of sulfur dioxide and pH on nanoparticle characteristics. J Colloid and Interface Science, 1992, 154(1): 77-86.
[8]	Uefuji K, Ichikura T, Mochizuki H. Expression of cyclooxygenase-2 in human gastric adenomas and adenocarcinomas. J Surg Oncol, 2001, 76(1): 26-30.
[9]	Williams C S, Tsujii M, Reese J, et a1. Host cyclooxygenase-2 modulates carcinoma growth. J Clin Invest, 2000, 105(11): 1589-1594.
[10]	Schmitt M, Horbach A, Kubitz R, et al. Disruption of hepatocellular tight junctions by vascular endothelial growth factor (VEGF): a novel mechanism for tumor invasion. J Hepatol, 2004, 41(2): 274-283.
[11]	Kawamori T, Lubet R, Steele V E, et al. Chemopreventive effect of curcumin, a naturally occurring anti-inflammatory agent, during the promotion/progression stages of colon cancer. Cancer Res, 1999, 59(3): 597-601.
[12]	Aggarwa B B, Kumar A, Bharti A C, et al. Anticancer potential of curcumin: preclinical and clinical studies. Anticancer Res, 2003, 23: 363-398.
[13]	Chen W F, Deng S L, Zhou B, et al. Curcumin and its analogues as potent inhibitors of low density lipoprotein oxidation: H-atom abstraction from the phenolic groups and possible involvement of the 4-hydroxy-3-methoxyphenyl groups. Free Radical Biology and Medicine, 2006, 40(3): 526-535.
[14]	Nurfina A N, Reksohadiprodjo M S, Timmerman H, et al. Synthesis of some symmetrical curcumin derivatives and their anti-inflammatory activity. Eur J Med Chem, 1997, 32(4): 321-328.
[15]	梁广,田吉来,邵丽丽,等. 姜黄素的构效关系及以其为先导物的抗肿瘤化合物研究进展. 化学通报,2008,71(2):110-117. Liang G, Tian J L, Shao L L, et al. Chemistry, 2008, 71(2):110-117.
[16]	张正全, 陆彬. 微乳给药系统研究概况. 中国医药工业杂志, 2001, 32(3): 139-142. Zhang Z Q, Lu B. Chinese J Pharmaceuticals, 2001, 32(3): 139-142.
[17]	胡俊, 刘玉玲. 载药纳米粒的研究进展. 中国医药工业杂志, 2004, 35(5): 310-314. Hu J, Liu Y L.Chinese J Pharmaceuticals, 2004, 35(5): 310-314.

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