| Objective:To observe the influence of Sorafenib and Arsenic trioxide to the FLT3-ITDpositive primary leukemia cells, to explore the mechanism of the combination of thetwo drugs, and to provide experimental basis for clinical treatment to FLT3-ITDpositive leukemia patients.Methods:1. The method of CCK-8was undertaken to test the inhibition effect ofSorafenib and Arsenic trioxide to the FLT3-ITD positive primary leukemia cells; andto test the effect of the combination of the two drugs.2. Flow cytometer was used to analyze the apoptosis of primary leukemia cells.3. The method of western blot was employed to test the change of AKT protein.Results:1. Sorafenib can inhibit the proliferation of FLT3-ITD positive primary leukemiacells, and the inhibition rate increased gradually with dose-increasing.2. Arsenic trioxide can inhibit the proliferation of FLT3-ITD positive and negativeprimary leukemia cells, the inhibition rate increased gradually with dose-increasing.3. The combination of Sorafenib and Arsenic trioxide can inhibit the proliferation ofFLT3-ITD positive synergistically.4. Both Sorafenib and Arsenic trioxide can induce apoptosis of FLT3-ITD positiveprimary leukemia cells, the combination of two drugs has a synergistic effect.5. Both Sorafenib and Arsenic trioxide can inhibit the AKT phosphorylation ofMV-4-11cell lines, the combination of two drugs can produce a sharper inhibition.Conclusions:1. Sorafenib can inhibit the proliferation of FLT3-ITD positive primary leukemiacells, with dose dependent manner.2. Both Sorafenib and Arsenic trioxide have impacts on the proliferation andapoptosis of FLT3-ITD positive primary leukemia cells, and the combination of twodrugs has a synergistic effect. 3. Both Sorafenib and Arsenic trioxide can inhibit the AKT phosphorylation ofMV-4-11cell lines.The PI3K/AKT signal channel is one of the most importantpathway of Sorafenib combination with Arsenic trioxide on the FLT3-ITD positiveleukemia cells. |
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