title: Effect of all-trans retinoic acid on the differentiation of U87 glioma stem/progenitor cells.
abstract: GSPCs (glioma stem/progenitor cells) were isolated from U87 glioma cell lines by serum-free neural stem cell medium. Four concentrations (1, 2, 4, and 8 μmol/L) of ATRA (all-trans retinoic acid) were used to induce the differentiation of GSPCs in the medium with or without growth factors. The effect of ATRA on the differentiation of GSPCs was analyzed by flow cytometry, real-time-PCR, and immunofluorescence. The differentiation of GSPCs could be induced by 1 or 2 μmol/L ATRA when GSPCs were cultured in growth factor-free medium. The detection of real-time-PCR showed that the level of GFAP (glial fibrillary acidic protein) mRNA of differentiated GSPCs in the growth factor-free medium containing 1 μmol/L ATRA group was significantly higher than that in the control group, and there was no significant difference in the level of TUBB-3 mRNA between the two groups. The GSPCs suffered apoptosis in the growth factor-free medium containing 4 or 8 μmol/L ATRA. The differentiation of GSPCs could not be induced by ATRA when GSPCs were cultured in the medium containing growth factors. The percentage of cells in G0/G1 phase was 84.26 ± 2.24 %, and the percentage of apoptosis was 18.95 ± 2.53 % in experimental groups which was similar to those in the control group. In conclusion, ATRA has certain capacity to induce differentiation of GSPCs, while its effective concentration should be controlled strictly. The differentiation of GSPCs induced by ATRA cannot antagonize the formidable differential inhibition of epidermal growth factor and basic fibroblast growth factor.
authors.affiliation: Department of Neurosurgery, Shanghai Tenth People's Hospital, Tongji University, No. 301 Middle Yanchang Road, Zabei District, Shanghai, 200072, China.
authors.forename: Zhe
authors.initials: Z
authors.lastname: Shi
authors.forename: Meiqing
authors.initials: M
authors.lastname: Lou
authors.forename: Yaodong
authors.initials: Y
authors.lastname: Zhao
authors.forename: Quanbin
authors.initials: Q
authors.lastname: Zhang
authors.forename: Daming
authors.initials: D
authors.lastname: Cui
authors.forename: Ke
authors.initials: K
authors.lastname: Wang
mesh_terms: D017209:Apoptosis / Q000187:drug effects / Q000235:genetics; D001932:Brain Neoplasms / Q000235:genetics / Q000473:pathology*; D002448:Cell Adhesion / Q000187:drug effects; D002454:Cell Differentiation / Q000187:drug effects* / Q000235:genetics; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D005455:Fluorescent Antibody Technique; D016193:G1 Phase / Q000187:drug effects / Q000235:genetics; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D005904:Glial Fibrillary Acidic Protein / Q000235:genetics / Q000378:metabolism; D005910:Glioma / Q000235:genetics / Q000473:pathology*; D006801:Humans; D014411:Neoplastic Stem Cells / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D016192:Resting Phase, Cell Cycle / Q000187:drug effects / Q000235:genetics; D018874:Spheroids, Cellular / Q000187:drug effects / Q000473:pathology; D014212:Tretinoin / Q000494:pharmacology*; D014404:Tubulin / Q000235:genetics / Q000378:metabolism
chemical_list: D005904:Glial Fibrillary Acidic Protein; D012333:RNA, Messenger; C498585:TUBB3 protein, human; D014404:Tubulin; D014212:Tretinoin