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[Inducing Effect of Akt Kinase Inhibitor MK2206 on Apoptosis in U937 Cells and RS4;11 Cells, and Its Mechanism].
- Source :
-
Zhongguo shi yan xue ye xue za zhi [Zhongguo Shi Yan Xue Ye Xue Za Zhi] 2015 Jun; Vol. 23 (3), pp. 627-32. - Publication Year :
- 2015
-
Abstract
- Objective: This study was purposed to investigate the effect of Akt kinase inhibitor MK2206 on proliferation and apoptosis of U937 cells and RS4;11 cells, and to explore its possible mechanism.<br />Methods: U937 and RS4;11 cells were cultured with different concentrations of MK2206 for 24 h and 48 h, and cell growth curve was analyzed by CCK-8; cell apoptosis was analyzed by Annexin V/7-AAD double labeling; cell cycle changes were analyzed by flow cytometry. The BAX, BCL-2, XIAP, CDK1, caspase-3 mRNA expressions were determined by real time PCR.<br />Results: MK2206 significantly inhibited the growth of U937 and RS4;11 cells in a time-and dose-dependent manner, and the IC50 values of U937 cells for 24 h and 48 h were (0.48±0.15) µmol/L and (0.09±0.01) µmol/L respectively, while IC50 values of RS4;11 cells for 24 h and 48 h were (0.91±0.02) µmol/L and (0.68±0.11) µmol/L respectively. U937 were cultured with 0.5 µmol/L MK2206 and RS4;11 cells were cultured with 1.0 µmol/L MK2206 for 24 h and 48 h, and the both apoptosis rates were higher for 24 h or 48 h than that in control group (P<0.05), meanwhile the apoptosis rates for 48 h were higher than 24 h. The results of cell cycle detection showed that the both cells were arrested in G2/M phase compared with control group. The real time PCR assay revealed that the expressions of BAX, caspase-3 mRNA in cells treated with MK2206 were increased, while BCL-2, XIAP, CDK1 were reduced compared with control group.<br />Conclusion: MK2206 can inhibit proliferation and induce apoptosis of U937 and RS4;11 cells, and the both cells are arrested in G2/M phase. The mechanism of promoting apoptosis may be related with up-regulating BAX, caspase-3 and down-regulating BCL-2, XIAP, meanwhile the cell cycle arrested in G2/M phase may be associated with down-regulating CDK1.
Details
- Language :
- Chinese
- ISSN :
- 1009-2137
- Volume :
- 23
- Issue :
- 3
- Database :
- MEDLINE
- Journal :
- Zhongguo shi yan xue ye xue za zhi
- Publication Type :
- Academic Journal
- Accession number :
- 26117006
- Full Text :
- https://doi.org/10.7534/j.issn.1009-2137.2015.03.005