10.6084/M9.FIGSHARE.C.4041281
Xin Zhang
Xin
Zhang
Shandong University
Xuehai Wang
Xuehai
Wang
Weihai Municipal Hospital
Ran Xu
Ran
Xu
Shandong University
Jianxiong Ji
Jianxiong
Ji
Shandong University
Yangyang Xu
Yangyang
Xu
Shandong University
Mingzhi Han
Mingzhi
Han
Shandong University
Yuzhen Wei
Yuzhen
Wei
Shandong University
Bin Huang
Bin
Huang
Shandong University
Anjing Chen
Anjing
Chen
Shandong University
Qing Zhang
Qing
Zhang
Shandong University
Wenjie Li
Wenjie
Li
Shandong University
Jian Wang
Jian
Wang
Shandong University
University of Bergen
Xingang Li
Xingang
Li
Shandong University
Chen Qiu
Chen
Qiu
Qilu Hospital of Shandong University
YM155 decreases radiation-induced invasion and reverses epithelial–mesenchymal transition by targeting STAT3 in glioblastoma
Abstract Background Radiotherapy constitutes a standard arm of therapy in the multimodal treatment of patients with glioblastoma (GBM). Ironically, studies have recently revealed that radiation can augment malignant progression, by promoting migration and invasion, which make the disease especially difficult to cure. Here, we investigated the anticancer effects of YM155, a purported radiosensitizer, in GBM cell lines. Methods GBM cell lines U251 and U87 were treated with YM155 to assess cytotoxicity and activity of the molecule in vitro. Nude mice were implanted with cells to generate orthotopic xenografts for in vivo studies. Response of cells to treatment was examined using cell viability, immunofluorescence, wound healing, and the Transwell invasion assay. Molecules potentially mediating response were examined through western blot analysis, phospho-kinase arrays, and qPCR. Cells were transfected with siRNA knockdown and gene expression constructs to identify molecular mediators of response. Results YM155 reduced viability of U251 and U87 cells and enhanced radiosensitivity through inhibition of homologous recombination. Besides, YM155 decreased invasion caused by radiation and led to expression changes in molecular markers associated with EMT. STAT3 was one of 10 molecules identified on a phosphokinase array exhibiting significant change in phosphorylation under YM155 treatment. Transfection with STAT3 siRNAs or expression constructs demonstrated that EMT changes were achieved by inhibiting the phosphorylation of STAT3 and were survivin-independent. Finally, combining YM155 and radiation in orthotopic xenografts reduced growth and prolonged overall survival of animals. Conclusions YM155 decreased radiation-induced invasion in GBM cell lines in vitro and in vivo through inhibition of STAT3.
Biochemistry
Cell Biology
Genetics
Molecular Biology
Chemical Sciences not elsewhere classified
Immunology
Biological Sciences not elsewhere classified
Developmental Biology
Cancer
figshare
2021
2021-09-25
2021-09-25
Collection
CC BY 4.0