Chinese Medical Sciences Journal ›› 2014, Vol. 29 ›› Issue (3): 174-179.doi: 10.1016/S1001-9294(14)60064-X

• Orginal Article • Previous Articles     Next Articles

ZM-66, a New Podophyllotoxin Derivative Inhibits Proliferation and Induces Apoptosis in K562/ADM Cells

Ling Li1, Hong-jie Li2, Jian-sheng zhi3, Hong Chen1, Wen-li Xie1, *   

  1. 1Department of Pharmacology, Logistics University of Chinese People’s Armed Police Forces, Tianjin 300309, China; 2Department of Oral Pathology, Stomatological Hospital, Tianjin Medical University, Tianjin 300309, China; 3Department of Anatomy, Tianjin Medical University, Tianjin 300309, China
  • Online:2014-09-29 Published:2014-09-29
  • Contact: *Corresponding author Tel: 86-22-84876734, E-mail: liling5257@126.com E-mail:liling5257@126.com
  • Supported by:
    △Supported by the Great Program of Science Foundation of Tianjin (08JCYBJC070000), the Program of Science Foundation of Tianjin (06YFJZJCO2700), and the National Natural Science Foundation of China (30873363)

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.

Key words: ZM-66, podophyllotoxin, multidrug resistance, P-glycoprotein, apoptosis

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