Anti-Leukemia Effect and Mechanism of Oridonin on Imatinib-Sensitive and Imatinib-Resistant K562 Cells / 中国实验血液学杂志

ABSTRACT

<p><b>OBJECTIVE</b>To explore the molecular mechanism of resistance to imatinib in K562 cells(K562-R) and the anti-proliferative effect of oridonin (OR), as well as its mechanism in imatinib-sensitive and imatinib-resistant K562 cells (K562-S and K562-R cells).</p><p><b>METHODS</b>The expression of p-Lyn in K562-S and K562-R cells were detected by Western blot. The anti-proliferative effect of OR in K562-S and K562-R cells was assayed by MTT, the morphological changes were examined with microscope, the cell apoptosis was detected by flow cytometry, the expressions of BCL-2 and Akt/mTOR signaling pathway were detected by Western blot.</p><p><b>RESULTS</b>The over-expression of p-Lyn was detcected in K562-R cells, OR inhibited the proliferation of K562-S and K562-R cells and the value of ICwas 4.23±1.30, 4.97±2.23 µmol/L, respectively. The apoptotic rate was obviously enhanced after OR treatment for 24 h, compared with control group. OR down-regulated the expression of p-Lyn, mTOR signaling pathway and BCL-2 protein.</p><p><b>CONCLUSION</b>Over-expression of p-Lyn may be involved in the mechanism of resistance to imatinib. OR can inhibit the proliferation of K562-S and K562-R cells through down-regulating p-Lyn, inhibiting mTOR signaling pathway and down-regulating expression of BCL-2 protein.</p>