title: BMP4 reverses multidrug resistance through modulation of BCL-2 and GDNF in glioblastoma.
abstract: Patients with glioblastoma are commonly treated with chemotherapy. But a significant proportion of patients develop disease progression after an initial response to chemotherapy. Presently, there is no standard of care for such patients. The bone morphogenetic protein 4 (BMP4) has been reported to play a tumor-suppressing role in glioblastoma, but its role in glioblastoma multidrug resistance (MDR) is not clear. We reported that BMP4 can reverse MDR of glioblastoma through the inhibition of B-cell lymphoma 2(BCL-2) and glial cell derived neurotrophic factor (GDNF). We showed that the expression level of BMP4 was lower in glioblastoma compared to normal brain tissue, and also showed that BMP4 expression decreased in multidrug resistance cell line U251/TMZ compared to U251 cells. Our research demonstrated that over-expression of BMP4 can reverse the multidrug resistance. BCL-2 and GDNF were inhibited when BMP4 was over-expressed, and this data were consistent with the negative relationship in human samples; analysis of 40 patient's glioblastoma and brain samples revealed a significant negative correlation between BMP4 and BCL-2, GDNF. When BCL-2 and GDNF were knocked down, the effect of BMP4 in regulating MDR was partially lost. This novel result showed, for the first time, that BMP4 can reverse MDR in glioblastoma, which involved negative inhibition of BCL-2 and GDNF.
authors: Renmin Hospital, Wuhan University, 238 Jiefang Street, Wuhan 430060, Hubei, China.
authors: Baohui
authors: B
authors: Liu
authors: Qianxue
authors: Q
authors: Chen
authors: Daofeng
authors: D
authors: Tian
authors: Liquan
authors: L
authors: Wu
authors: Huimin
authors: H
authors: Dong
authors: Junmin
authors: J
authors: Wang
authors: Baowei
authors: B
authors: Ji
authors: Xiaonan
authors: X
authors: Zhu
authors: Qiang
authors: Q
authors: Cai
authors: Long
authors: L
authors: Wang
authors: Shenqi
authors: S
authors: Zhang
mesh_terms: D000328:Adult; D000368:Aged; D000818:Animals; D055415:Bone Morphogenetic Protein 4 / Q000378:metabolism*; D001932:Brain Neoplasms / Q000378:metabolism*; D045744:Cell Line, Tumor; D018432:Drug Resistance, Multiple; D019008:Drug Resistance, Neoplasm; D051100:Glial Cell Line-Derived Neurotrophic Factor / Q000378:metabolism*; D005909:Glioblastoma / Q000378:metabolism*; D006801:Humans; D008297:Male; D051379:Mice; D008875:Middle Aged; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism*; D055815:Young Adult
chemical_list: C525809:BMP4 protein, human; D055415:Bone Morphogenetic Protein 4; D051100:Glial Cell Line-Derived Neurotrophic Factor; D019253:Proto-Oncogene Proteins c-bcl-2