title: Abraxane, the Nanoparticle Formulation of Paclitaxel Can Induce Drug Resistance by Up-Regulation of P-gp.
abstract: 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.
authors.affiliation: CAS Key Laboratory for Biological Effects of Nanomaterials and Nanosafety, National Center for Nanoscience and Technology, Chinese Academy of Sciences, Beijing, 100190, China.
authors.forename: Minzhi
authors.initials: M
authors.lastname: Zhao
authors.affiliation: CAS Key Laboratory for Biological Effects of Nanomaterials and Nanosafety, National Center for Nanoscience and Technology, Chinese Academy of Sciences, Beijing, 100190, China.
authors.forename: Chunni
authors.initials: C
authors.lastname: Lei
authors.affiliation: CAS Key Laboratory of Genome Sciences and Information, Beijing Institute of Genomics, Chinese Academy of Sciences, Beijing, 100101, China.
authors.forename: Yadong
authors.initials: Y
authors.lastname: Yang
authors.affiliation: CAS Key Laboratory for Biological Effects of Nanomaterials and Nanosafety, National Center for Nanoscience and Technology, Chinese Academy of Sciences, Beijing, 100190, China.
authors.forename: Xiangli
authors.initials: X
authors.lastname: Bu
authors.affiliation: CAS Key Laboratory for Biological Effects of Nanomaterials and Nanosafety, National Center for Nanoscience and Technology, Chinese Academy of Sciences, Beijing, 100190, China.
authors.forename: Huailei
authors.initials: H
authors.lastname: Ma
authors.affiliation: CAS Key Laboratory for Biological Effects of Nanomaterials and Nanosafety, National Center for Nanoscience and Technology, Chinese Academy of Sciences, Beijing, 100190, China.
authors.forename: He
authors.initials: H
authors.lastname: Gong
authors.affiliation: CAS Key Laboratory for Biological Effects of Nanomaterials and Nanosafety, National Center for Nanoscience and Technology, Chinese Academy of Sciences, Beijing, 100190, China.
authors.forename: Juan
authors.initials: J
authors.lastname: Liu
authors.affiliation: CAS Key Laboratory of Genome Sciences and Information, Beijing Institute of Genomics, Chinese Academy of Sciences, Beijing, 100101, China.
authors.forename: Xiangdong
authors.initials: X
authors.lastname: Fang
authors.affiliation: CAS Key Laboratory for Biological Effects of Nanomaterials and Nanosafety, National Center for Nanoscience and Technology, Chinese Academy of Sciences, Beijing, 100190, China; Beijing Proteome Research Center, Beijing Institute of Radiation Medicine, Beijing, 102206, China.
authors.forename: Zhiyuan
authors.initials: Z
authors.lastname: Hu
authors.affiliation: CAS Key Laboratory for Biological Effects of Nanomaterials and Nanosafety, National Center for Nanoscience and Technology, Chinese Academy of Sciences, Beijing, 100190, China.
authors.forename: Qiaojun
authors.initials: Q
authors.lastname: Fang
mesh_terms: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000235:genetics* / Q000378:metabolism; D000068196:Albumin-Bound Paclitaxel / Q000737:chemistry / Q000494:pharmacology*; D000972:Antineoplastic Agents, Phytogenic / Q000737:chemistry / Q000494:pharmacology*; D002121:Calcium Channel Blockers / Q000494:pharmacology; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D004339:Drug Compounding; D019008:Drug Resistance, Neoplasm / Q000187:drug effects / Q000235:genetics*; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D058977:Molecular Sequence Annotation; D005810:Multigene Family; D053758:Nanoparticles / Q000737:chemistry*; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism; D020545:Respiratory Mucosa / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D015398:Signal Transduction; D059467:Transcriptome; D014700:Verapamil / Q000494:pharmacology
chemical_list: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000068196:Albumin-Bound Paclitaxel; D000972:Antineoplastic Agents, Phytogenic; D002121:Calcium Channel Blockers; D020033:Protein Isoforms; D014700:Verapamil