I have an experiment about stat3 inhibitors effect on leukemia cells. And I want to leukemia cells will be alive after 2 days stat3 inhibitor effect. Do you have any opinion or experience about this situation? Does stat3 have impact of death on leukemia cells?
http://www.ncbi.nlm.nih.gov/pubmed/25394909
http://www.ncbi.nlm.nih.gov/pubmed/25368256
Just go to pubmed and search for STAT3 inhibition and apoptosis. STAT3 is an important protein involved in proliferation pathway, I would guess that its blockage will induce apoptosis after some time.
You have to go for some kind of time/concentration killing curve by titration as the apoptotic effect will definitely occur depending on your drug concentration - maybe if you use a low concentration the cells will be still alive after 2-3 days, but apoptosis will definitely be one reaction of the cells.
The leukemia cell response to STAT3 inhibitors will depend on how this cell depend on STAT3 to maintain the malignant phenotype. There are several leukemic strains lacking the pathway activity JAK/STAT altered. I suggest you to test different cell lines and check the profile of STAT3 activity among the cell lines that respond or not to STAT3 inhibitor. The cell line HEL, which possesses the JAK2 V617F and responds to Ruxolitinib (a JAK inhibitor), may become a control for your experiments.
Well, to find a good answer to your question is very hard. First of all which AML cell lines do you use? Primary human or mouse?
And what genetic/biochemical background do you want to investigate?
In our lab we use different murine and primary human AML cell lines with different mutations including FLT3-ITD mutation.
Perhaps you should first have a look on the activation of different STAT isoforms to be sure, that STAT3 is the best target for pharmacologic intervention. However, a inhibitor is a good aproach to test your hypothesis. But you have to be sure, that your inhibitor does not have side effects, like interfering with other proteins. So you might also check the specificty of your inhibitor. Perhaps you also try a knockdown in your cell lines to make a clearer statement on the role of STAT3 in your approaches.
So perhaps you could write more details to your project.
Kind regards
Thank you Christian for your information and suggestion. I am working with human AML cell lines and use Stat3 Inhibitor V (Santa Cruz Biotechnology). Finally, ı optimized stat3 inhibitor's concentration. And ı can work with these cells while their stat3 pathway is inactive and they are alive.