title: Perifosine downregulates MDR1 gene expression and reverses multidrug-resistant phenotype by inhibiting PI3K/Akt/NF-κB signaling pathway in a human breast cancer cell line.
abstract: P-glycoprotein (P-gp)-mediated multidrug resistance (MDR) is the major clinical impediment to chemotherapy of breast cancers. Down-regulation of PI3K/Akt pathway has been described as related to reversal of MDR in cancer cells. Here, we investigated the reversal effect on MDR phenotype of perifosine, a new Akt inhibitor, in breast cancer cell lines. In this study, MCF-7/ADM cells and MCF-7 cells were treated with different concentrations of perifosine. Our results suggested that perifosine reversed MDR partially by downregulation of P-gp expression and inhibition of PI3K/Akt/NF-κB pathway in the MCF-7/ADM cell line. The novel Akt inhibitor perifosine may be a promising new drug due to its ability to reverse MDR in human breast cancer cells.
authors.affiliation: Department of Pathology, Provincial Hospital affiliated to Shandong University, Jinan, China.
authors.forename: X
authors.initials: X
authors.lastname: Lin
authors.forename: X
authors.initials: X
authors.lastname: Zhang
authors.forename: Q
authors.initials: Q
authors.lastname: Wang
authors.forename: J
authors.initials: J
authors.lastname: Li
authors.forename: P
authors.initials: P
authors.lastname: Zhang
authors.forename: M
authors.initials: M
authors.lastname: Zhao
authors.forename: X
authors.initials: X
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; D017209:Apoptosis / Q000187:drug effects; D015153:Blotting, Western; D001943:Breast Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000378:metabolism*; D045744:Cell Line, Tumor; D002467:Cell Nucleus / Q000235:genetics / Q000378:metabolism; D049109:Cell Proliferation / Q000187:drug effects; D015536:Down-Regulation; D018432:Drug Resistance, Multiple / Q000187:drug effects*; D019008:Drug Resistance, Neoplasm / Q000187:drug effects; D053492:Elafin / Q000037:antagonists & inhibitors* / Q000378:metabolism; D005260:Female; D005434:Flow Cytometry; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D016328:NF-kappa B / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D010767:Phosphorylcholine / Q000031:analogs & derivatives* / Q000494:pharmacology; D051057:Proto-Oncogene Proteins c-akt / Q000037:antagonists & inhibitors* / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D015398:Signal Transduction / Q000187:drug effects; D014407:Tumor Cells, Cultured
chemical_list: C513055:ABCB1 protein, human; D018435:ATP Binding Cassette Transporter, Subfamily B; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D053492:Elafin; D016328:NF-kappa B; C506806:PI3 protein, human; D012333:RNA, Messenger; D010767:Phosphorylcholine; C105905:perifosine; D051057:Proto-Oncogene Proteins c-akt