Induction Of PI13K/Akt Pathway In SHI₁ Cells Of Acute Myelogenous Leukemia By Bo9rtezomib In Vitro

OBJECTIVE By investigating the effect of Bortezomib on proliferation and apoptosis of SHI₁ cells and detecting the protein expression of PI3K,P-Akt,caspase-3. To explore the mechanism of myeloid leukemia cells induced by bortezomib.METHODS SHI₁ cells were treated with bortezomib in different concentrations(5,50,100,150 ng/ml). MTT assay and flow cytometry were used to detect the proliferation inhibition and apoptosis. Western blotting was used to detect the protein expression of PI3K,P-Akt,caspase-3.RESULTS 5- 100 ng/ml bortezomib could effectively inhibit SHI₁ cell proliferation and induce its apoptosis. With time prolongation and dose increasing, SHI₁ cell apoptotic rate significantly increased (P<0.01). After treating for 12 hours, 50 ng/ml bortezomib could inhibit cell proliferation. Furthermore, Bortezomib could induce SHI₁ cell proliferation in the manner of time–dose dependen(tP<0.01). When SHI₁ cells were treated by different doses of bortezomib after 24 hours, PI3K and P-Akt protein expression were down-regulated and the expression of 150ng/ml was the least. While caspase-3 was up-regulated in a dose-dependent.CONCLUSION The mechanism of Bortezomib to induce apoptosis of myeloid leukemia cells is probably associated with down-regulation of PI3K and P-Akt protein expression and increasing caspase3 activities.