Knockdown of diacylglycerol kinase zeta (DGKZ) induces apoptosis and G2/M phase arrest in human acute myeloid leukemia HL-60 cells through MAPK/survivin/caspase pathway.

Diacylglycerol kinase zeta (DGKZ) is associated with the pathogenesis of a variety of malignant diseases, but its biological function on acute myeloid leukemia (AML) has not been explored. The aim of this study was to analyze apoptosis induced by knockdown of DGKZ and its mechanism in human acute myeloid leukemia HL-60 cells. qRT-PCR was carried out to detect the expression of DGKZ in HL-60, THP-1, Jurkat, K562, and CD34 cell lines. Additionally the expression of DGKZ in AML cells obtained from patients were detected by qRT-PCR. Cell Counting Kit-8 (CCK-8) assay was used to determine the viability of HL-60 cells DGKZ knocked down. Apoptosis and cell cycle phase of HL-60 cells after DGKZ knockdown were evaluated by flow cytometry. Western blot analysis was performed to investigate expressions of the proteins related to apoptosis and cell cycle. Results showed that expression of DGKZ was significantly higher in HL-60 and AML cells obtained from patients than those of Jurkat, THP-1, K562 and human CD34 cell. Compared with the shCtrl group, DGKZ was markedly knocked down in HL-60 cells transfected with lentivirus encoding shRNA. DGKZ knockdown significantly inhibited the proliferation and induced cycle arrest at the G2/M phase in HL-60 cells. The expressions of MAPK, caspase-3, caspase-8, cytochrome C markedly increased and p-MAPK and survivin decreased in HL-60 cells after DGKZ knockdown. The results suggest that knockdown of DGKZ can induce apoptosis and G2/M phase arrest in human acute myeloid leukemia HL-60 cells through the MAPK/survivin/caspase pathway.

Citation

Hong Li, Changhu Dong, Yanning Tian, Xiang Li, Bing Wang, Dongzhi Zhai, Yingying Bai, Xu Chao. Knockdown of diacylglycerol kinase zeta (DGKZ) induces apoptosis and G2/M phase arrest in human acute myeloid leukemia HL-60 cells through MAPK/survivin/caspase pathway. Die Pharmazie. 2019 Jul 01;74(7):418-422

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PMID: 31288898

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