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Albumin Nanoparticle of Paclitaxel (Abraxane) Decreases while Taxol Increases Breast Cancer Stem Cells in Treatment of Triple Negative Breast Cancer.
Molecular Pharmaceutics ( IF 4.5 ) Pub Date : 2020-06-02 , DOI: 10.1021/acs.molpharmaceut.9b01221
Hebao Yuan 1 , Hongwei Guo 1 , Xin Luan 1 , Miao He 1 , Feng Li 1 , Joseph Burnett 1 , Nathan Truchan 1 , Duxin Sun 1
Affiliation  

Triple-negative breast cancer (TNBC) has a high rate of metastasis, which is associated with breast cancer stem-like cells (CSCs). Although Taxol (micelle formulation of paclitaxel) is the first line chemotherapy to treat TNBC, it increases CSCs in residual tumors. Abraxane, albumin nanoparticle of paclitaxel, showed lower plasma concentration compared to Taxol in both human and animal models, but it is not clear why Abraxane showed superior efficacy to Taxol in treatment of metastatic breast cancer in humans. In this study, we intend to investigate if Abraxane eliminates CSCs for its better efficacy. The results showed that Abraxane showed similar cytotoxicity in SUM149 cells in comparison with Taxol. Although Abraxane showed 3- to 5-fold lower blood drug concentration compared to Taxol, it achieved similar tumor drug concentration and 10-fold higher tumor/plasma ratio in SUM149 xenograft NOD/SCID mouse model. In addition, Abraxane and Taxol showed similar efficacy to shrink the tumor size in orthotopic breast cancer NOD/SCID mouse model. However, Abraxane decreased breast CSCs frequency by 3- to 9-fold, while Taxol increased breast CSCs frequency in an orthotopic breast cancer NOD/SCID mouse model. Furthermore, Abraxane increased 3- to 15-fold intracellular uptake in both ALDH+ CSCs and differentiated ALDH– cells in comparison with Taxol, which provides a mechanism for Abraxane’s superior efficacy to eliminate CSCs in comparison with Taxol. Our data suggest albumin nanoparticle Abraxane may have a broad implication to enhance drug’s efficacy by eliminating breast cancer stem cells for treatment of metastatic diseases.

中文翻译:

紫杉醇(Abraxane)的白蛋白纳米颗粒减少而紫杉醇增加乳腺癌干细胞治疗三阴性乳腺癌。

三阴性乳腺癌 (TNBC) 具有高转移率,这与乳腺癌干细胞样细胞 (CSC) 相关。尽管紫杉醇(紫杉醇的胶束制剂)是治疗 TNBC 的一线化疗药物,但它会增加残留肿瘤中的 CSC。与紫杉醇相比,紫杉醇的白蛋白纳米颗粒 Abraxane 在人类和动物模型中的血浆浓度低于紫杉醇,但尚不清楚为什么 Abraxane 在治疗人类转移性乳腺癌方面表现出优于紫杉醇的功效。在这项研究中,我们打算调查 Abraxane 是否会因其更好的功效而消除 CSC。结果表明,与紫杉醇相比,Abraxane 在 SUM149 细胞中显示出相似的细胞毒性。尽管 Abraxane 的血液药物浓度比紫杉醇低 3 到 5 倍,它在 SUM149 异种移植 NOD/SCID 小鼠模型中实现了相似的肿瘤药物浓度和高 10 倍的肿瘤/血浆比率。此外,Abraxane 和紫杉醇在原位乳腺癌 NOD/SCID 小鼠模型中显示出相似的缩小肿瘤大小的功效。然而,在原位乳腺癌 NOD/SCID 小鼠模型中,Abraxane 将乳腺 CSC 频率降低了 3 到 9 倍,而紫杉醇增加了乳腺 CSC 频率。此外,与紫杉醇相比,Abraxane 在 ALDH+ CSC 和分化的 ALDH- 细胞中的细胞内摄取增加了 3 至 15 倍,这为 Abraxane 与紫杉醇相比消除 CSC 的卓越功效提供了一种机制。我们的数据表明,白蛋白纳米颗粒 Abraxane 可能对通过消除乳腺癌干细胞治疗转移性疾病来增强药物疗效具有广泛的意义。
更新日期:2020-07-06
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