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    许河南, 王月月, 陈天天, 闫雷, 王文锐, 杨清玲, 陈昌杰. 紫杉醇长循环纳米胶束的制备及其对乳腺癌多药耐药的研究[J]. 蚌埠医科大学学报, 2019, 44(9): 1142-1147. DOI: 10.13898/j.cnki.issn.1000-2200.2019.09.002
    引用本文: 许河南, 王月月, 陈天天, 闫雷, 王文锐, 杨清玲, 陈昌杰. 紫杉醇长循环纳米胶束的制备及其对乳腺癌多药耐药的研究[J]. 蚌埠医科大学学报, 2019, 44(9): 1142-1147. DOI: 10.13898/j.cnki.issn.1000-2200.2019.09.002
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    XU He-nan, WANG Yue-yue, CHEN Tian-tian, YAN Lei, WANG Wen-rui, YANG Qing-ling, CHEN Chang-jie. Preparation of paclitaxel long-circulating nanomicelles and their multidrug resistance to breast cancer[J]. Journal of Bengbu Medical University, 2019, 44(9): 1142-1147. DOI: 10.13898/j.cnki.issn.1000-2200.2019.09.002
    Citation: XU He-nan, WANG Yue-yue, CHEN Tian-tian, YAN Lei, WANG Wen-rui, YANG Qing-ling, CHEN Chang-jie. Preparation of paclitaxel long-circulating nanomicelles and their multidrug resistance to breast cancer[J]. Journal of Bengbu Medical University, 2019, 44(9): 1142-1147. DOI: 10.13898/j.cnki.issn.1000-2200.2019.09.002
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    紫杉醇长循环纳米胶束的制备及其对乳腺癌多药耐药的研究

    Preparation of paclitaxel long-circulating nanomicelles and their multidrug resistance to breast cancer

      摘要
    • 摘要:
      目的制备紫杉醇长循环胶束TPGS-PEG2000-DSPE-PTX，探讨紫杉醇胶束对乳腺癌MCF-7紫杉醇耐药细胞（MCF-7/PR）增殖、凋亡、迁移和侵袭的影响。
      方法采用薄膜分散法制备负载紫杉醇的TPGS-PEG2000-DSPE-PTX胶束，对载药胶束进行形貌、粒径、电位等表征分析；采用磺酰罗丹明B染色法、Annexin V/PI染色法以及划痕和transwell实验检测紫杉醇胶束对乳腺癌耐药细胞株增殖、凋亡、迁移和侵袭的影响。
      结果成功构建了紫杉醇载药胶束，透射电镜可见载药胶束成圆球形，粒径30~40 nm，Zeta电位为-5.4 mV，紫外分光光度计检测并计算载药量为25.37%。与对照组和紫杉醇组比较，紫杉醇胶束组有效抑制耐药细胞的增殖、迁移和侵袭，诱导细胞凋亡，上调caspase3和Bax的蛋白表达水平（P < 0.01），下调Bcl-2、P-糖蛋白和多药耐药相关蛋白的表达水平（P < 0.01）。
      结论成功构建TPGS修饰的紫杉醇长循环胶束给药系统，可有效在体外发挥抗肿瘤效应及逆转多药耐药作，为开发新型的抗癌药物给药系统提供了参考依据。

       

      Abstract:
      ObjectiveTo prepare paclitaxel long-circulating micelle TPGS-PEG2000-DSPE-PTX and investigate the effects of paclitaxel micelles on proliferation, apoptosis, migration and invasion of paclitaxel-resistant cells (MCF-7/PR) in breast cancer.
      MethodsThe paclitaxel-loaded TPGS-PEG2000-DSPE-PTX micelles were prepared by membrane dispersion method.The morphology, particle size and potential of the drug-loaded micelles were characterized..The sulfonyl rhodamine B method, flow cytometry and migration were performed.Sulfonylrhodamine B staining, Annexin V/PI staining, scratch and transwell assays were used to detect the effects of paclitaxel micelles on proliferation, apoptosis, migration, and invasion of paclitaxel resistant cell lines.
      ResultsPaclitaxel-loaded micelles were successfully constructed.The results of transmission electron microscopy showed that the drug-loaded micelles became spherical, with a particle size of 30-40 nm and a zeta potential of -5.4 mV.The UV spectrophotometer detected and calculated the drug loading amount to 25.37%.Compared with the control group and the paclitaxel group, the TPGS-PEG2000-DSPE-PTX group effectively inhibited the proliferation, migration and invasion of drug-resistant cells, induced apoptosis, up-regulated the protein expression levels of caspase3 and Bax(P < 0.01), and down-regulated Bcl-2, P-gp and MRP protein expression levels(P < 0.01).
      ConclusionsThe successful construction of TPGS modified paclitaxel long-circulating micelle delivery system can effectively exert anti-tumor effect and reverse multi-drug resistance in vitro, and provide a reference for the development of a new anti-cancer drug delivery system.

       

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