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Your search keyword '"Wei-Wei Du"' showing total 2 results
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2 results on '"Wei-Wei Du"'

1. Inhibition of neuroblastoma proliferation by PF-3758309, a small-molecule inhibitor that targets p21-activated kinase 4

Author

Xiaolu Li, Li-Xiao Xu, Xiaolan Chen, Wei-Wei Du, Guang-Hui Qian, Chun Yang, Yi Wu, Jian Wang, Shaoyan Hu, He Zhao, Jian Pan, Fang Fang, Jun Lu, Xin Ding, Junli Ren, Zhi-Heng Li, Mei Li, Yunyun Xu, and Yan-Fang Tao

Subjects
Adult, Male, 0301 basic medicine, Cancer Research, Cell cycle checkpoint, Cell Survival, MAP Kinase Signaling System, Cell, Biology, neuroblastoma, 03 medical and health sciences, Cell Line, Tumor, Neuroblastoma, medicine, Humans, Pyrroles, Protein Kinase Inhibitors, Cell Proliferation, Neoplasm Staging, Oncogene, Kinase, Cell Cycle, apoptosis, Articles, General Medicine, Cell cycle, medicine.disease, Up-Regulation, Cell biology, Gene Expression Regulation, Neoplastic, PF-3758309, growth arrest, 030104 developmental biology, medicine.anatomical_structure, p21-Activated Kinases, Oncology, PAK4, Apoptosis, Cancer cell, Cancer research, Pyrazoles, Female
Abstract

Neuroblastoma is the most common extracranial solid childhood tumor. Despite the availability of advanced multimodal therapy, high-risk patients still have low survival rates. p21-activated kinase 4 (PAK4) has been shown to regulate many cellular processes in cancer cells, including migration, polarization and proliferation. However, the role of PAK4 in neuroblastoma remains unclear. In the present study, we demonstrated that PAK4 was overexpressed in neuroblastoma tissues and was correlated with tumor malignance and prognosis. To investigate the function of PAK4 in neuroblastoma, we used a small-molecule inhibitor that targets PAK4, that is, PF-3758309. Our results showed that PF-3758309 significantly induced cell cycle arrest at the G1 phase and apoptosis in neuroblastoma cell lines. Meanwhile, the inhibition of PAK4 by PF-3758309 increased the expression of CDKN1A, BAD and BAK1 and decreased the expression of Bcl-2 and Bax. In addition, we screened the target genes of PAK4 by PCR array and found that 23 genes were upregulated (including TP53I3, TBX3, EEF1A2, CDKN1A, IFNB1 and MAPK8IP2) and 20 genes were downregulated (including TNFSF8, Bcl2-A1, Bcl2L1, SOCS3, BIRC3 and NFKB1) after PAK4 inhibition by PF-3758309. Moreover, PAK4 was found to regulate the cell cycle and apoptosis via the ERK signaling pathway. In conclusion, the present study demonstrated, for the first time, the expression and function of PAK4 in neuroblastomas and the inhibitory effect of PF-3758309, which deserves further investigation as an alternative strategy for neuroblastoma treatment.

Published
2017

2. Molecular mechanism of G1 arrest and cellular senescence induced by LEE011, a novel CDK4/CDK6 inhibitor, in leukemia cells.

Author

Yan-Fang Tao, Na-Na Wang, Li-Xiao Xu, Zhi-Heng Li, Xiao-Lu Li, Yun-Yun Xu, Fang Fang, Mei Li, Guang-Hui Qian, Yan-Hong Li, Yi-Ping Li, Yi Wu, Jun-Li Ren, Wei-Wei Du, Jun Lu, Xing Feng, Jian Wang, Wei-Qi He, Shao-Yan Hu, and Jian Pan

Subjects
CELLULAR aging, CYCLIN-dependent kinase inhibitors, LEUKEMIA, GENETIC overexpression, GALACTOSIDASES, APOPTOSIS
Abstract

Background: Overexpression of cyclin D1 dependent kinases 4 and 6 (CDK4/6) is a common feature of many human cancers including leukemia. LEE011 is a novel inhibitor of both CDK4 and 6. To date, the molecular function of LEE011 in leukemia remains unclear. Methods: Leukemia cell growth and apoptosis following LEE011 treatment was assessed through CCK-8 and annexin V/propidium iodide staining assays. Cell senescence was assessed by β-galactosidase staining and p16INK4a expression analysis. Gene expression profiles of LEE011 treated HL-60 cells were investigated using an Arraystar Human LncRNA array. Gene ontology and KEGG pathway analysis were then used to analyze the differentially expressed genes from the cluster analysis. Results: Our studies demonstrated that LEE011 inhibited proliferation of leukemia cells and could induce apoptosis. Hoechst 33,342 staining analysis showed DNA fragmentation and distortion of nuclear structures following LEE011 treatment. Cell cycle analysis showed LEE011 significantly induced cell cycle G1 arrest in seven of eight acute leukemia cells lines, the exception being THP-1 cells. β-Galactosidase staining analysis and p16INK4a expression analysis showed that LEE011 treatment can induce cell senescence of leukemia cells. LncRNA microarray analysis showed 2083 differentially expressed mRNAs and 3224 differentially expressed lncRNAs in LEE011-treated HL-60 cells compared with controls. Molecular function analysis showed that LEE011 induced senescence in leukemia cells partially through downregulation of the transcriptional expression of MYBL2. Conclusions: We demonstrate for the first time that LEE011 treatment results in inhibition of cell proliferation and induction of G1 arrest and cellular senescence in leukemia cells. LncRNA microarray analysis showed differentially expressed mRNAs and lncRNAs in LEE011-treated HL-60 cells and we demonstrated that LEE011 induces cellular senescence partially through downregulation of the expression of MYBL2. These results may open new lines of investigation regarding the molecular mechanism of LEE011 induced cellular senescence. [ABSTRACT FROM AUTHOR]

Published
2017
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