ZM-66, a New Podophyllotoxin Derivative Inhibits Proliferation and Induces Apoptosis in K562/ADM Cells |
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Authors: | Ling Li Hong-jie Li Jian-sheng zhi Hong Chen Wen-li Xie |
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Institution: | 1. Department of Pharmacology, Logistics University of Chinese People’s Armed Police Forces, Tianjin 300309, China 2. Department of 0ral Pathology, Stomatological Hospital, Tianjin Medical University, Tianjin 300309, China 3. Department of Anatomy, Tianjin Medical University, Tianjin 300309, China |
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Abstract: | Objective To investigate the anti-tumor effect of ZM-66 on multidrug-resistant leukemic cell line K562/ADM. Methods The K562/ADM cells were treated with varying concentrations (0, 1, 2, 4×10-3 mmol/L) of ZM-66 or etoposide for 24 hours. The proliferation was detected by Sulforhodamine B Sodium Salt (SRB) assay and apoptosis was detected by flow cytometry analysis and fluorescent staining. In addition, the expression levels of p53 and bax genes in K562/ADM cells were detected by RT-PCR analysis. The level of P-glycoprotein (P-gp), P53 and Bax protein in K562/ADM cells were detected by Western blot assay. Results SRB assay demonstrated that etoposide had little inhibitory effect on K562/ADM cells, whereas ZM-66 (1, 2, 4×10-3 mmol/L) had significantly inhibitory effect on K562/ADM cells (all P<0.01). The acridine orange/propidium iodide dual staining showed that there were typical condensation of chromatin and nuclear fragmentation nuclei with red color in ZM-66 treated cells. Flow cytometric analysis showed that there was a significantly increase of apoptotic cells in K562/ADM cells after treated with ZM-66. RT-PCR showed that the p53 and bax mRNA expression levels in K562/ADM cells treated with ZM-66 at 1, 2, 4×10-3 mmol/L were higher than those in the cell without treatment. Western blot showed that the P53 and Bax protein expression levels in K562/ADM cells treated with ZM-66 at 2, 4×10-3 mmol/L were higher than those in the cell without treatment. But the P-gp protein expression level in K562/ADM cells treated with ZM-66 at 2, 4×10-3 mmol/L was gradually lower than those in the cell without treatment. Conclusion ZM-66 is able to induce cell death by apoptosis in vitro, as a result of the reverse of the apoptosis resistance in drug-resistant K562/ADM cells by modulating expression of key factors associated with apoptosis induction. |
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Keywords: | ZM-66 podophyllotoxin multidrug resistance P-glycoprotein apoptosis |
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