title: Signal transduction pathways and transcriptional mechanisms of ABCB1/Pgp-mediated multiple drug resistance in human cancer cells.
abstract: Multiple drug resistance (MDR), defined as the ability of tumour cells to survive exposure to many chemotherapeutic agents, is a major cause of treatment failure in human cancers. The membrane transporter P-glycoprotein (Pgp, encoded by the ABCB1 [adenosine triphosphate-binding  cassette, subfamily B, member 1] gene) is the main mechanism for decreased intracellular drug accumulation in human MDR cancer. ABCB1/Pgp-mediated MDR involves several signal transduction pathways and transcription factors. Activation of these signal transduction pathways influences  the prognosis of MDR human cancer. Signalling pathways involved in ABCB1/Pgp-mediated MDR include the mitogen-activated protein kinase (MAPK), c-Jun NH(2)-terminal kinase (JNK), p38, cyclic adenosine monophosphate-dependent protein kinase, phosphatidylino sitol 3-kinase and  protein kinase C signalling pathways. This review summarizes the biological characteristics, target points and signalling cascade mediators of these pathways. Drugs targeted against these pathways may provide new therapies for treatment of ABCB1/Pgp-mediated MDR.
authors.affiliation: Interventional Cancer Institute of Chinese Integrative Medicine, Putuo Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, China.
authors.forename: H
authors.initials: H
authors.lastname: Sui
authors.forename: Z-Z
authors.initials: ZZ
authors.lastname: Fan
authors.forename: Q
authors.initials: Q
authors.lastname: Li
mesh_terms: D018435:ATP Binding Cassette Transporter, Subfamily B; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000235:genetics / Q000378:metabolism*; D000970:Antineoplastic Agents / Q000378:metabolism / Q000627:therapeutic use; D001692:Biological Transport / Q000235:genetics; D018432:Drug Resistance, Multiple / Q000235:genetics / Q000502:physiology*; D019008:Drug Resistance, Neoplasm / Q000235:genetics; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism; D020935:MAP Kinase Signaling System / Q000235:genetics / Q000502:physiology*; D009369:Neoplasms / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism*; D058539:Phosphatidylinositol 3-Kinase / Q000378:metabolism; D011493:Protein Kinase C / Q000378:metabolism; D014158:Transcription, Genetic; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
chemical_list: C513055:ABCB1 protein, human; D018435:ATP Binding Cassette Transporter, Subfamily B; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000970:Antineoplastic Agents; D058539:Phosphatidylinositol 3-Kinase; D011493:Protein Kinase C; D048031:JNK Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases