中国病理生理杂志2012，Vol.28Issue(1)：59-64,6.DOI:10.3969/j.issn.1000-4718.2012.01.011
胶质瘤细胞维甲酸代谢调控机制及其对细胞增殖的影响
Metabolic mechanism of retinoic acid in glioma cells and its impact on cell proliferation
摘要
Abstract
AIM:To investigate the mechanism for regulating the synthesis and metabolism of retinoic acid in glioma cell line SWO -Z2 and its effect on cell proliferation. METHODS:The siRNA targeting to human KLF9 mRNA was transfected into SWO - Z2 cells. The silencing efficiency was detected by real -time PCR and Western blotting. After silencing of KLF9, the protein level of ALDH1 Al was detected by Western blotting. CCK - 8 colorimetric assay was used to screen the optimal concentration of retinoic acid, and the strongest inhibitory effect of retinoic acid from 3 types of chemicals ,13 - cis - retinoic acid ( 13 - cis RA ), 9 - cis - retinoic acid (9 - cis RA ) and all - trans retinoic acid ( ATRA ), on SWO - Z2 cell growth was selected. Western blotting was also applied to explore the expression levels of cyclin Dl, Bel - 2, cleaved PARP and GFAP in SWO - Z2 cells with the treatment of ATRA for 72 h. Simultaneously, the mRNA levels of retinoic acid receptors ( RARs ) in SWO - Z2 cells were determined by real - time PCR. RESULTS: siRNA - KLF9 knocked - down the expression of KLF9 and down - regulated the expression of aldehyde dehydrogenase 1 family member Al ( ALDH1A1 ) at mRNA and protein levels ( P <0. 05 ). Among the 3 retinoic acid drugs, ATRA was the most effective in inhibiting the proliferation of SWO - Z2 cells.After treated with ATRA on SWO - Z2 cells for 72 h, the expression ofcleaved PARP was increased, Bel -2 and cyclin Dl were decreased, and GFAP didn't change. The mRNA level of RARs in SWO - Z2 cells was very low. CONCLUSION: KLF9 positively regulates the expression of ALDH1 Al gene to increase the synthesis of retinoic acid. ATRA inhibits proliferation but does not induce differentiation of SWO - Z2 cells, which might result from lack of retinoic acid receptors in human glioma cells.关键词
Krüpple样转录因子9/全反式维甲酸/受体,维甲酸/醛脱氢酶1家族成员A1/细胞分化Key words
Kriipple-like transcription factor 9/All-trans retinoic acid/Receptors,retinoic acid/Aldehyde dehydrogenase 1 family member Al/Cell differentiation分类
医药卫生引用本文复制引用
张继君,谢思明,林琛莅,翁泽平,杜展,王超,钟雪云..胶质瘤细胞维甲酸代谢调控机制及其对细胞增殖的影响[J].中国病理生理杂志,2012,28(1):59-64,6.基金项目
国家自然科学基金资助项目(No.81072059) （No.81072059）
国家自然科学基金青年基金资助项目(No.81101652) （No.81101652）
广东省自然科学基金资助项目(No.10151063201000059) （No.10151063201000059）
暨南大学科研培育与创新基金青年基金资助项目(No.216113122). （No.216113122）
