Open AccessSignal Transduction Pathways and Transcriptional Mechanisms of ABCB1/Pgp-mediated Multiple Drug Resistance in Human Cancer Cells
Author(s) -
Sui H,
Fan Zz,
Li Q
Publication year - 2012
Publication title -
journal of international medical research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.421
H-Index - 57
eISSN - 1473-2300
pISSN - 0300-0605
DOI - 10.1177/147323001204000204
Subject(s) - signal transduction , kinase , protein kinase a , biology , atp binding cassette transporter , microbiology and biotechnology , cancer research , mapk/erk pathway , medicine , pharmacology , biochemistry , transporter , gene
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, phosphatidylinositol 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.