Abstract
Abstract 4381
Background:
Homoharringtonine (HHT) was efficient in therapying patients with acute myeloid leukemia (AML) in China, but little is known about the mechanism of its action. The phosphatidylinositol 3-kinase (PI3K)/Akt/mammalian target of rapamycin (mTOR) signaling axis plays a central role in cell proliferation, growth, and survival under physiological conditions and many human cancers, including acute myelogenous leukemia (AML). We try to explore the effect of HHT on PI3K/Akt pathway in AML cells, thus supplying theoretical basis for wider use of HHT.
Method:
The NB4 and SHI-1 cells were cultured in 20% FCS RPMI-1640 with different concentration of HHT, cell proliferation was detected with MTT, apoptosis was measured by FCM, the protein of PI3K and p-Akt were determined by Western blot.
Result:
5ug/L HHT suppressed NB4 and SHI-1 cells proliferation and induced apoptosis after culture 24hr, 100ug/L HHT suppressed 71.29% NB4 and 64.83% SHI-1 cells proliferation respectively. Apoptosis increased obviously with the increasing HHT concentration and the culture time, the leukemia cell apoptosis was significant at 500ug/L HHT, about 41.84% NB4 cells and 46.88% SHI-1 cells were apoptosis when the HHT concentration was 100ug/L. The protein expression of PI3K, and p-Akt gradually declined with HHT concentration increasing, when 500ug/L HHT co-cultured with leukemia cells for 24 hours, The protein expression of PI3K and p-Akt were lowest. The p-Akt of NB4 and SHI-1 cells decreased 28.4% and 34.5% respectively at 5ug/L HHT for 48hr, the PI3K of NB4 and SHI-1 cells decreased 31.56% and 37.38% respectively at 10ug/L HHT for 48hr.
Conclusion:
HHT could inhibit NB4, SHI-1 cells proliferation and induce leukemia cells apoptosis, and could down-regulate the expression of PI3K and p-Akt significantly, this might be the one of mechanisms that HHT induce NB4 and SHI-1 cells apoptosis, we presume that HHT inhibit proliferation of acute myelogenous leukemia cells through effect of PI3K/Akt signaling pathways.
Disclosures:
No relevant conflicts of interest to declare.
Studying The Right Cell In Acute Myelogenous Leukemia: Dynamic Changes Of Apoptosis And Signal Transduction Pathway Protein Expression In Chemotherapy Resistant Ex-Vivo Selected “Survivor Cells”