Anti-Tumor Effect of Rigosertib on HEL and K562 Cells and Its Related Mechanism / 中国实验血液学杂志

ABSTRACT

<p><b>OBJECTIVE</b>To investigate the effects of rigosertib on the apoptosis, proliferation and cell cycle of HEL and K562 cells.</p><p><b>METHODS</b>The HEL and K562 cells were treated with different concentration of rigosertib at different time points, the cell apoptosis, proliferation and cycle were determined by using flow cytometry with Annexin V/PI double staining, WST-1 method and 7-AAD assay, respectively. Intracellular signaling proteins were detected by flow cytometry (FCM).</p><p><b>RESULTS</b>Rigosertib induced obvious apoptosis in HEL and K562 cells, and the apoptotic effect was both time-dependent and dose-dependent manner (P<0.05). The low dose of rigosertib inhibited obviously the proliferation of HEL and K562 cells after treatment from 6 to 54 h, Rigosertib arrested HEL and K562 cells into G/M phase. In addition, Rigosertib obviously increased the expression of apoptosis-related proteins such as cleaved caspase 3 and PARP, and reduced the proliferation-related proteins such as BCL-2 and Cyclin D1. Rigosetib inhibited the activation of AKT-GSK signaling through decreasing the expression of AKT, pAKT(Ser473) and GSK-3α/β (S21/9).</p><p><b>CONCLUSION</b>Rigosertib inhibites proliferation, induces apoptosis and cell cycle arrest in G/M phase of HEL and K562 cells. This agent may have potential application prospect in leukemia therapy.</p>