title: Knockdown of the potential cancer stem-like cell marker Rex-1 improves chemotherapeutic effects in gliomas.
abstract: In the present study, we show that Rex-1 mRNA and protein are found at high levels in both 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU)-resistant glioma cell subpopulations and malignant glioblastoma multiforme (GBM) tissue. We used a combination therapy of small interfering RNA (siRNA) against Rex-1 (siRex-1) and BCNU to target GBM cells. Rex-1 siRNA/BCNU treatment resulted in growth inhibition and a diminished S phase. The treatment efficiently induced P38/JNK and Akt/PI3K/GSK3β signaling and led to apoptosis both in vitro and in vivo. We also show that Rex-1/ABCG2 (ATP binding cassette transporter G2)-coexpressing subpopulations were chemoresistant; however, BCNU was not a substrate for ABCG2. siRex-1 treatment led to cell death in GBM subpopulations by promoting apoptosis. Moreover, siRex-1/BCNU combination therapy targeted both the major population and cancer stem cell-like subpopulations. Our findings are important for the development of clinical applications to treat GBM.
authors.affiliation: Laboratory of Stem Cell Biology, Department of Biotechnology, Seoul National University, Seoul 151-742, Republic of Korea.
authors.forename: Bong-Sun
authors.initials: BS
authors.lastname: Kim
authors.forename: Kyung-Sun
authors.initials: KS
authors.lastname: Kang
authors.forename: Jee-In
authors.initials: JI
authors.lastname: Choi
authors.forename: Jin-Sun
authors.initials: JS
authors.lastname: Jung
authors.forename: Young-Bin
authors.initials: YB
authors.lastname: Im
authors.forename: Soo-Kyung
authors.initials: SK
authors.lastname: Kang
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use; D017209:Apoptosis; D015153:Blotting, Western; D001932:Brain Neoplasms / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism; D002330:Carmustine / Q000627:therapeutic use*; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D019175:DNA Methylation; D019008:Drug Resistance, Neoplasm / Q000235:genetics*; D005260:Female; D005910:Glioma / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D007124:Immunoenzyme Techniques; D051741:Kruppel-Like Transcription Factors / Q000037:antagonists & inhibitors* / Q000235:genetics; D051379:Mice; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D014411:Neoplastic Stem Cells / Q000378:metabolism / Q000473:pathology; D011401:Promoter Regions, Genetic; D012333:RNA, Messenger / Q000235:genetics; D034741:RNA, Small Interfering / Q000235:genetics*; D060888:Real-Time Polymerase Chain Reaction; D014407:Tumor Cells, Cultured
chemical_list: D000970:Antineoplastic Agents; D051741:Kruppel-Like Transcription Factors; D012333:RNA, Messenger; D034741:RNA, Small Interfering; C507976:ZFP42 protein, human; D002330:Carmustine