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通过负载叠氮紫杉醇的抗肿瘤人血清白蛋白纳米粒抑制三阴性乳腺癌细胞的增殖、迁移和侵袭,叠氮紫杉醇为一种新型紫杉烷衍生物。

Inhibiting the proliferation, migration and invasion of triple negative breast cancer cells through anti-tumor human serum albumin nanoparticles loading aziditaxel as a novel taxane derivative.

作者信息

Chen Li-Qing, Zhang Zhe-Ming, Huang Wei, Gao Zhong-Gao, Fang Wei-Shuo, Jin Ming-Ji, Yu Lian

出版信息

Pharmazie. 2017 Mar 1;72(3):152-160. doi: 10.1691/ph.2017.6146.

DOI:10.1691/ph.2017.6146
PMID:29442050
Abstract

Triple negative breast cancer (TNBC) is a severe breast cancer subtype with the high mortality rate, and still is lack of effective therapeutic means so far. Aziditaxel, a water-insoluble compound, is a novel taxane derivative with strong anti-tumor activity. In this study, we constructed an aziditaxel-loaded nano drug delivery system using human serum albumin as a carrier, and further investigated its anti-tumor effect on TNBC in vitro. An emulsion solvent evaporation method was employed to prepare aziditaxel-loaded human serum albumin nanoparticles (AT-NPs). Their physicochemical properties were characterized according to morphology, particle size, zeta potential, reconstitution stability and in vitro drug release. The in vitro anti-tumor effects of AT-NPs on TNBC were evaluated using a 4T1 murine triple negative mammary cancer cell lines as the TNBC model. The results showed that AT-NPs could be effectively taken up by 4T1 cells in a time-dependent manner. Cell Counting Kit-8 assay showed that the IC50 of AT-NPs was 0.17 μg/ml. Meanwhile, compared with AT, AT-NPs had a better ability to promote apoptosis and induce G2/M cycle arrest. On the other hand, AT-NPs had significantly inhibitory effects on the 4T1 cell adhesion, migration and invasion with the respective average inhibition ratios of 32.53%, 83.26% and 75.78%. Thus, our study revealed that AT-NPs had favorable antitumor activity in vitro and exhibited a good prospect for application in the field of TNBC therapy.

摘要

三阴性乳腺癌(TNBC)是一种死亡率高的严重乳腺癌亚型,迄今为止仍缺乏有效的治疗手段。叠氮紫杉醇是一种水不溶性化合物,是一种具有强大抗肿瘤活性的新型紫杉烷衍生物。在本研究中,我们以人血清白蛋白为载体构建了负载叠氮紫杉醇的纳米药物递送系统,并进一步研究了其对TNBC的体外抗肿瘤作用。采用乳化溶剂蒸发法制备负载叠氮紫杉醇的人血清白蛋白纳米粒(AT-NPs)。根据形态、粒径、zeta电位、复溶稳定性和体外药物释放对其理化性质进行了表征。以4T1小鼠三阴性乳腺癌细胞系为TNBC模型,评价了AT-NPs对TNBC的体外抗肿瘤作用。结果表明,AT-NPs能被4T1细胞以时间依赖性方式有效摄取。细胞计数试剂盒-8检测显示,AT-NPs的IC50为0.17μg/ml。同时,与AT相比,AT-NPs具有更好的促进凋亡和诱导G2/M期阻滞的能力。另一方面,AT-NPs对4T1细胞的黏附、迁移和侵袭具有显著的抑制作用,平均抑制率分别为32.53%、83.26%和75.78%。因此,我们的研究表明,AT-NPs在体外具有良好的抗肿瘤活性,在TNBC治疗领域具有良好的应用前景。

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