Xia Shi-Lin, Wu Mo-Li, Li Hong, Wang Jia-Hui, Chen Nan-Nan, Chen Xiao-Yan, Kong Qing-You, Sun Zheng, Liu Jia
Liaoning Laboratory of Cancer Genetics and Epigenetics and Department of Cell Biology, College of Basic Medical Sciences, Dalian Medical University, Dalian, China.
Department of Hematology, PLA 210 Hospital, Dalian, China.
Oncotarget. 2015 Mar 20;6(8):5889-902. doi: 10.18632/oncotarget.3334.
Glioblastomas respond differently to all-trans retinoic acid (RA) for unknown reasons. Because CRABP-II and FABP5 mediate RA intracellular signaling respectively and lead to distinct biological consequences, their expression patterns in different grades of astrocytomas and the glioblastoma cells lines LN18, LN428 and U251 were examined to identify potential correlations with RA sensitivities. The response of glioblastoma cells to RA, decitabine or the FABP5 competitive inhibitor, BMS309403, was analyzed. CRABP-II and FABP5 were expressed to varying degrees by the 84-astrocytoma cases examined. Treatment of LN428, U251 and LN18 cells with RA failed to suppress their growth; however, U251 proliferation was inhibited by decitabine. The combination of decitabine and RA suppressed the growth of all three cell lines and induced significant apoptosis of LN428 and U251 cells. Both CRABP-II and FABP5 were transcribed in the three cell lines but FABP5 proteins were undetectable in U251 cells. The ratio of CRABP-II to FABP5 was not altered after RA, decitabine or RA and decitabine treatment and the resistance of cells to RA was not reversed by BMS309403 treatment. In conclusion, CRABP-II and FABP5 expression patterns are neither related to the tumor grades nor correlated with RA sensitivity. Additional molecular factors may be present that determines the sensitivity of glioblastoma cells to RA. Dicitabine may improve the sensitivity of glioblastoma cells to RA, however, its underlying mechanism and its in vivo feasibility need to be investigated.
胶质母细胞瘤对全反式维甲酸（RA）的反应因不明原因而有所不同。由于细胞视黄酸结合蛋白-II（CRABP-II）和脂肪酸结合蛋白5（FABP5）分别介导RA的细胞内信号传导并导致不同的生物学后果，因此检测了它们在不同级别星形细胞瘤以及胶质母细胞瘤细胞系LN18、LN428和U251中的表达模式，以确定与RA敏感性的潜在相关性。分析了胶质母细胞瘤细胞对RA、地西他滨或FABP5竞争性抑制剂BMS309403的反应。在所检测的84例星形细胞瘤病例中，CRABP-II和FABP5的表达程度各不相同。用RA处理LN428、U251和LN18细胞未能抑制其生长；然而，地西他滨抑制了U251细胞的增殖。地西他滨和RA联合使用抑制了所有三种细胞系的生长，并诱导LN428和U251细胞发生显著凋亡。三种细胞系中均转录了CRABP-II和FABP5，但在U251细胞中未检测到FABP5蛋白。RA、地西他滨或RA与地西他滨联合处理后，CRABP-II与FABP5的比例未发生改变，且BMS309403处理未逆转细胞对RA的耐药性。总之，CRABP-II和FABP5的表达模式既与肿瘤分级无关，也与RA敏感性无关。可能存在其他分子因素决定胶质母细胞瘤细胞对RA的敏感性。地西他滨可能会提高胶质母细胞瘤细胞对RA的敏感性，然而，其潜在机制及其体内可行性有待研究。
