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

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。

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

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.