Higher LRRFIP1 expression in glioblastoma multiforme is associated with better response to teniposide, a type II topoisomerase inhibitor

Previous studies from this laboratory indicated that microRNA-21 (miR-21) contributes to chemoresistance of glioblastoma multiforme (GBM) cells to teniposide, a type II topoisomerase inhibitor. We also showed that LRRFIP1 is a target of miR-21. In this study, we found that higher baseline LRRFIP1 expression in human GBM tissue (n = 60) is associated with better prognosis upon later treatment with teniposide. Experiments in cultured U373MG cells showed enhanced toxicity of teniposide against U373MG cells transfected with a vector that resulted in LRRFIP1 overexpression (vs. cells transfected with control vector). Experiments in nude mice demonstrated better response of LRRFIP1 overexpressing xenografts to teniposide. These findings indicate that high baseline LRRFIP1 expression in GBM is associated with better response to teniposide, and encourage exploring LRRFIP1 as a target for GBM treatment. (C) 2014 Elsevier Inc. All rights reserved.

本实验室先前的研究表明，微小RNA - 21（miR - 21）导致多形性胶质母细胞瘤（GBM）细胞对替尼泊苷（一种II型拓扑异构酶抑制剂）产生耐药性。我们还发现LRRFIP1是miR - 21的一个靶标。在这项研究中，我们发现人GBM组织（n = 60）中较高的基线LRRFIP1表达与后续使用替尼泊苷治疗时较好的预后相关。在培养的U373MG细胞中进行的实验表明，替尼泊苷对转染了导致LRRFIP1过表达的载体的U373MG细胞（相较于转染对照载体的细胞）毒性增强。在裸鼠中进行的实验表明，LRRFIP1过表达的异种移植物对替尼泊苷有更好的反应。这些研究结果表明，GBM中较高的基线LRRFIP1表达与对替尼泊苷更好的反应相关，并鼓励将LRRFIP1作为GBM治疗的一个靶点进行探索。（C）2014爱思唯尔公司。保留所有权利。