1. Dual PLK1 and STAT3 inhibition promotes glioblastoma cells apoptosis through MYC
- Author
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Haoran Yin, Hao Wang, Zibin Feng, Zhennan Tao, Xuetao Li, Guangliang Chen, Zhitong Deng, Yanyan Li, Youxin Zhou, Tingzheng Pan, Guozheng Zhao, and Ming Feng
- Subjects
0301 basic medicine ,Carcinogenesis ,Apoptosis ,Cell Cycle Proteins ,medicine.disease_cause ,Biochemistry ,Mice ,0302 clinical medicine ,Cell Movement ,RNA, Small Interfering ,STAT3 ,biology ,Brain Neoplasms ,Chemistry ,Kinase ,Pteridines ,Cyclic S-Oxides ,Tumor Burden ,Gene Expression Regulation, Neoplastic ,030220 oncology & carcinogenesis ,Female ,Neuroglia ,Signal Transduction ,STAT3 Transcription Factor ,Biophysics ,Brain tumor ,Mice, Nude ,Antineoplastic Agents ,Protein Serine-Threonine Kinases ,PLK1 ,Proto-Oncogene Proteins c-myc ,03 medical and health sciences ,Cell Line, Tumor ,Proto-Oncogene Proteins ,Glioma ,medicine ,Animals ,Humans ,Molecular Biology ,Cell Proliferation ,Cell Biology ,medicine.disease ,Survival Analysis ,Xenograft Model Antitumor Assays ,030104 developmental biology ,biology.protein ,STAT protein ,Cancer research ,Glioblastoma - Abstract
Glioblastoma (GBM) is the deadliest primary brain tumor that is highly resistant to current treatments. Polo-like kinase 1 (PLK1) and signal transducer and activator of transcription 3 (STAT3) are highly expressed in gliomas, especially GBM. Previous studies have shown reciprocal activation between PLK1 and STAT3 and that they regulate the same pools of MYC downstream. We have demonstrated that PLK1 and STAT3 levels are elevated in gliomas compared with those in normal brain tissues, and high expression of both PLK1 and STAT3 is associated with poor prognosis in TCGA. Moreover, there was direct or indirect reciprocal regulation between PLK1 and STAT3. Furthermore, we found that PLK1 and STAT3 can regulate the same pools of MYC downstream. Compared to monotherapy, combined treatment of glioma cells with PLK1 and STAT3 inhibitors, BI2536 and Stattic, respectively, showed lower expression of MYC, synergistic induction of cell invasion and apoptosis in vitro, and tumor inhibition in xenografts. PLK1 and STAT3 were able to directly regulate the expression of MYC and induce apoptosis of glioma cells through the regulation of MYC. These findings may help develop a therapeutic strategy for dual inhibition of PLK1 and STAT3 against the tumorigenesis of glioma.
- Published
- 2020
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