CRABP-II- and FABP5-independent responsiveness of human glioblastoma cells to all-trans retinoic acid
PDF | HTML | How to cite
Metrics: PDF 2141 views | HTML 2485 views | ?
Shi-Lin Xia1,*, Mo-Li Wu1,*, Hong Li1, Jia-Hui Wang1, Nan-Nan Chen2, Xiao-Yan Chen1, Qing-You Kong1, Zheng Sun1 and Jia Liu1
1 Liaoning Laboratory of Cancer Genetics and Epigenetics and Department of Cell Biology, College of Basic Medical Sciences, Dalian Medical University, Dalian, China
2 Department of Hematology, PLA 210 Hospital, Dalian, China
* These authors contributed equally to this work
Jia Liu, email:
Keywords: Glioblastoma, All-trans retinoic acid, Chemosensitivity, CRABP-II, FABP5
Received: September 24, 2014 Accepted: January 05, 2015 Published: January 21, 2015
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.
All site content, except where otherwise noted, is licensed under a Creative Commons Attribution 3.0 License.