期刊
PLOS ONE
卷 10, 期 7, 页码 -出版社
PUBLIC LIBRARY SCIENCE
DOI: 10.1371/journal.pone.0131429
关键词
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资金
- National Natural Science Foundation of China [31270875, 31470049]
- Chinese Academy of Science [YZ201217, Y4362911ZX]
- International S&T Cooperation Program of China [2010DFB33880]
- State Key Development Program for Basic Research of China [2011CB915502]
- Strategic Priority Research Program of Chinese Academy of Sciences
- Stem Cell and Regenerative Medicine Research [XDA01040405]
- National Programs for High Technology Research and Development (863 Project) [2012AA022502]
- National Twelfth Five-Year Plan for Science & Technology Support [2013BAI01B09]
- Shanghai Leading Academic Discipline Project [B502]
- Shanghai Key Laboratory Project [08DZ2230500]
- Science and Technology Commission of Shanghai Municipality Project [11nm0507000]
- Scientific Research Foundation for Returned Overseas Chinese Scholars, State Education Ministry
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.
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