Salinomycin inhibits proliferation and induces apoptosis of Gleevec-resistant chronic myeloid leukemic cell line K562/Glv |
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| Authors: | XU Shuang-qing ZHU Ai-zhen LIU Cheng-cheng XU Ting-ting CHEN Xiao-yu LIU Ge-xiu |
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| Institution: | 1. Faculty of Laboratory Medicine, Xiangya Medical College of Central South University, Changsha 410013, China;2. Guangzhou Kingmed Diagnostics Center, Guangzhou 510330, China;3. Institute of Hematology, School of Medicine, Jinan University, Guangzhou 510632, China |
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| Abstract: | AIM: To study the effect of salinomycin on inhibiting proliferation and inducing apoptosis of Gleevec-resistant chronic myeloid leukemia cell line K562/Glv. METHODS: The inhibitory effect of salinomycin on the growth of K562/Glv cells was detected by CCK-8 assay in vitro. Flow cytometry was used to observe apoptosis, mitochondria membrane potential (ΔΨm), reactive oxygen species (ROS) and the concentration of intracellular Ca2+ (Ca2+]i) in K562/Glv cells. The activity of caspase-3, -8 and -9 was measured by the method of colorimetry. The levels of cytochrome C, Bcl-2, Bax, β-catenin and phosphorylated low-density lipoprotein receptor-related protein 6 (p-LRP6) were determined by Western blotting. RESULTS: Salinomycin inhibited the growth of K562/Glv cells in a dose-dependent manner. Salinomycin at concentration of 0.2 μmol/L inhibited the growth of the cells with the inhibitory rate of (36.70±2.31)%. The cell apoptotic rate was (19.66±2.23)%. Salinomycin at concentration of 0.2 μmol/L decreased the level of ΔΨm, and increased the levels of ROS, cytochrome C andCa2+]i in the cells. Salinomycin also increased the activity of caspase-3, -8 and -9 in the cells, reduced the ratio of Bcl-2/Bax, and attenuated the levels of β-catenin and p-LRP6. CONCLUSION: Salinomycin induces the apoptosis of Gleevec-resistant myeloid leukemia cell line K562/Glv via Bcl-2/Bax and mitochondria-dependent pathways, and inhibits the cell growth through Wnt signal pathway. |
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| Keywords: | Salinomycin Gleevec Leukemia Apoptosis Mitochondria β-catenin Low-density lipoprotein receptor-related protein 6 |
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