Abraxane, the Nanoparticle Formulation of Paclitaxel Can Induce Drug Resistance by Up-Regulation of P-gp.
Abraxane, the Nanoparticle Formulation of Paclitaxel Can Induce Drug Resistance by Up-Regulation of P-gp.
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Abraxane，紫杉醇纳米颗粒制剂可通过上调 P-gp 诱导耐药性
DOI：
10.1371/journal.pone.0131429
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发表时间：
2015
期刊：
影响因子：
3.7
通讯作者：
Fang Q
中科院分区：
文献类型：
--
作者：
Zhao M;Lei C;Yang Y;Bu X;Ma H;Gong H;Liu J;Fang X;Hu Z;Fang Q
P-glycoprotein (P-gp) can actively pump paclitaxel (PTX) out of cells and induces drug resistance. Abraxane, a nanoparticle (NP) formulation of PTX, has multiple clinical advantages over the single molecule form. However, it is still unclear whether Abraxane overcomes the common small molecule drug resistance problem mediated by P-gp. Here we were able to establish an Abraxane-resistant cell line from the lung adenocarcinoma cell line A549. We compared the transcriptome of A549/Abr resistant cell line to that of its parental cell line using RNA-Seq technology. Several pathways were found to be up or down regulated. Specifically, the most significantly up-regulated gene was ABCB1, which translates into P-glycoprotein. We verified the overexpression of P-glycoprotein and confirmed its function by reversing the drug resistance with P-gp inhibitor Verapamil. The results suggest that efflux pathway plays an important role in the Abraxane-resistant cell line we established. However, the relevance of this P-gp mediated Abraxane resistance in tumors of lung cancer patients remains unknown.
