GDC-0032 inhibits cell viability and induces DNA damage in U251 human glioma cells |
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| Authors: | CUI Hai-juan ZHANG Ya-yun JIAO Peng SUN Zheng |
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| Institution: | 1. School of Nursing, Taishan Medical University, Tai'an 271016, China;
2. The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, China;
3. Life Sciences Research Centre, Taishan Medical University, Tai'an 271000, China;
4. The Second School of Clinical Medicine, Taishan Medical University, Tai'an 271000, China |
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| Abstract: | AIM: To investigate the effect of phosphatidylinostiol 3-kinase (PI3K) inhibitor GDC-0032 on cell viability, cell cycle and DNA damage in human glioma U251 cells. METHODS: The cell viability was analyzed by MTT assay. The cell cycle distribution of U251 cells was examined by flow cytometry. The protein expression was examined by Western blot. The expression and localization of γ-H2AX were determined by laser-scanning confocal microscopy. RESULTS: GDC-0032 inhibited the cell viability in a dose-dependent manner. U251 cells showed G1 phase arrest accompanied with upregulation of p27 protein after exposure to GDC-0032, while the expression of cell division cycle protein 2 (Cdc2) was inhibited. GDC-0032 treatment increased the formation of γ-H2AX foci and histone H2AX phosphorylation in the U251 cells. In addition, GDC-0032 upregulated the phosphorylation levels of mitogen-activated protein kinases, including extracellular signal-regulated kinase (ERK) and c-Jun N-terminal kinase (JNK), in the glioma cells, while the expression of survivin was inhibited. CONCLUSION: GDC-0032 inhibits U251 cell growth by inhibition of cell viability and cell cycle progression. GDC-0032 also induces DNA damage of U251 cells. The anticancer activity of GDC-0032 is associated with increasing the activity of ERK and JNK and downregulating the expression of survivin. |
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| Keywords: | GDC-0032 Glioma Cell viability DNA damage Mitogen-activated protein kinases |
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