Key structure of brij for overcoming multidrug resistance in cancer.
Key structure of brij for overcoming multidrug resistance in cancer.
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DOI：
10.1021/bm301661w
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发表时间：
2013-02-11
影响因子：
6.2
通讯作者：
Liu, Feng
中科院分区：
文献类型：
--
作者：
Tang, Jingling;Wang, Yongjun;Wang, Dun;Wang, Yuhua;Xu, Zhenghong;Racette, Kelly;Liu, Feng
多药耐药（MDR）是许多癌症化疗的主要障碍。然而，一些非离子表面活性剂，例如Brij，已经显示出恢复MDR细胞对这些药物的敏感性。本研究旨在探讨Brij对多药耐药肿瘤细胞的逆转作用及其机制。我们的数据表明，Brij表面活性剂的结构在克服癌症MDR中起着重要作用，即改性的亲水亲油平衡（MHLB，环氧乙烷（EO）的亲水重复单元数（n）与疏水尾部（CH 2）中碳数（m）的比率）。用Brij配制的紫杉醇（PTX）纳米晶体（NC）处理的细胞的细胞活力与MHLB显示出正相关性（R2 = 0.8195）; NC中Brij与PTX的比率越高，PTX NC诱导的细胞毒性越高。在用Brij 78（MHLB=1.11）和Brij 97（MHLB=0.6）处理的MDR细胞系（H460/taxR细胞）中观察到3 H-PTX（P-gp底物）的细胞内蓄积显著增加。Brij 78和Brij 97处理后，多药耐药细胞内ATP水平降低，维拉帕米诱导的P-gp ATP酶活性受到抑制。在ATP耗竭研究中，细胞对Brij 78和Brij 97的反应与PTX/Brij NC诱导的细胞活力和3 H-PTX的细胞内蓄积相关。Western blotting检测到Brij 78和Brij 97不能改变P-gp的表达水平。这些发现可能为进一步开发更有效的P-gp抑制剂用于治疗癌症MDR的可能性提供一些见解。
Multidrug resistance (MDR) is a major barrier to the chemotherapy treatment of many cancers. However, some non-ionic surfactants, for example Brij, have been shown to restore the sensitivity of MDR cells to such drugs. The aim of this study was to explore the reversal effect of Brij on MDR tumor cells and elucidate its potential mechanism. Our data indicate that the structure of Brij surfactants plays an important role in overcoming MDR in cancer, i.e. modified hydrophilic-lipophilic balance (MHLB, the ratio of the number (n) of hydrophilic repeating units of ethylene oxide (EO) to the number (m) of carbons in the hydrophobic tail (CH2).). Cell viability of cells treated with paclitaxel (PTX) nanocrystals (NCs) formulated with Brij showed positive correlations with MHLB (R2 = 0.8195); the higher the ratio of Brij to PTX in NCs, the higher cytotoxicity induced by the PTX NCs. Significant increases in intracellular accumulation of 3H-PTX (P-gp substrate) were observed in an MDR cell line (H460/taxR cells) treated with Brij 78 (MHLB=1.11) and Brij 97 (MHLB=0.6). After treatments with Brij 78 and Brij 97, the levels of intracellular ATP were decreased and verapamil induced ATPase activities of P-gp were inhibited in multidrug resistant cells. The responses of the cells to Brij 78 and Brij 97 in ATP depletion studies correlated with the cell viability induced by PTX/Brij NCs and intracellular accumulation of 3H-PTX. Brij 78 and Brij 97 could not alter the levels of P-gp expression detected by western blotting. These findings may provide some insight into the likelihood of further development of more potent P-gp inhibitors for the treatment of MDR in cancer.
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影响因子：
4.9
作者：
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通讯作者：
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作者：
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