Messerli Shanta M, Hoffman Mariah M, Gnimpieba Etienne Z, Kohlhof Hella, Bhardwaj Ratan D
Sanford Children's Health Research Center, Department of Pediatrics, Cancer Biology and Immunotherapies, Sanford Research, Sanford School of Medicine, University of South Dakota, Vermillion, SD 57069, USA.
Biomedical Engineering Department, University of South Dakota, Vermillion, SD 57069, USA.
Brain Sci. 2017 Nov 3;7(11):147. doi: 10.3390/brainsci7110147.
This project involves an examination of the effect of the small molecule inhibitor 4SC-202 on the growth of the pediatric brain cancer medulloblastoma. The small molecule inhibitor 4SC-202 significantly inhibits the viability of the pediatric desmoplastic cerebellar human medulloblastoma cell line DAOY, with an IC = 58.1 nM, but does not affect the viability of noncancerous neural stem cells (NSC). 4SC-202 exposure inhibits hedgehog expression in the DAOY cell line. Furthermore, microarray analysis of human medulloblastoma patient tumors indicate significant upregulation of key targets in the Hedgehog signaling pathway and Protein Tyrosine Kinase (PTK7).
本项目涉及研究小分子抑制剂4SC - 202对小儿脑癌髓母细胞瘤生长的影响。小分子抑制剂4SC - 202能显著抑制小儿促结缔组织增生性小脑髓母细胞瘤细胞系DAOY的活力,其半数抑制浓度(IC)为58.1 nM,但不影响非癌性神经干细胞(NSC)的活力。4SC - 202处理可抑制DAOY细胞系中的刺猬信号通路表达。此外,对人类髓母细胞瘤患者肿瘤的微阵列分析表明,刺猬信号通路中的关键靶点和蛋白酪氨酸激酶(PTK7)显著上调。