Abstract
Objective To investigate the effect of all-trans retinoic acid (ATRA) on the proliferation and differentiation of brain tumor stem cells (BTSCs) in vitro. Methods Freshly resected glioblastoma multiforme tissues were obtained from 3 surgical patients, and BTSCs were isolated by limited dilution and clonogenic assay. The BTSCs obtained were cultured in serum-free medium and divided into control group, ATRA group, growth factor group, and ATRA/growth factor group with corresponding treatments. The proliferation of the treated BTSCs was evaluated using MTT assay. The BTSCs were induced in serum-containing medium and treated with ATRA or diluted solvent, and the expression of CD133 and glial fibrillary acidic protein (GFAP) in the cells were detected by immunofluorescence on day 10 of induction. The differentiated BTSCs were cultured in serum-flee medium, and the percentage of and time needed for cell sphere formation were observed. Results The proliferation of BTSCs in ATRA group was faster than that in the control group and slower than that in growth factor group and ATRA/growth factor group, and the size of brain tumor sphere (BTS) in ATRA group was smaller than that in the latter two groups. The percentage of CD133 and GFAP-positive differentiated BTSCs were (2.29±0.27)% and (75.60±4.03)% in ATRA group, and (7.05±0.49)% and (12.51±0.77)% in the control group, respectively. The differentiation rate of BTSCs was significantly higher in ATRA group than in the control group (P<0.05), and some of the differentiated BTSCs expressed CD133. The differentiated BTSCs could form BTS in serum-free medium, and in ATRA group, the percentage of BTS formation was significantly lower and time need for BTS formation was significantly longer than those in the control group [(4.84±0.32)% vs (17.71±0.78)%, P<0.05;10.07±1.03 vs 4.08±0.35 days, P<0.05]. Conclusion ATRA can promote the proliferation and induce the differentiation of BTSCs, but the differentiated BTSCs can not achieve terminal differentiation and tend to form BTS again. Key words: All-trans retinoic acid; Brain tumor stem cells; Proliferation; Differentiation
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