the interaction lies nearer to the zero line as indicated by the interaction parameter value of 0 revealing less strong synergy. 413 when compared with 0. 243 for the siRNA control cells. Three dimensional results were made. In the siRNA get a handle on cells, Fig. When compared to the GW0742 treated cells, Fig 4c, the top is more tightened toward the origin. 4d, indicating that the synergistic effect has been reduced after-treatment with siRNA for HSP70. There is no effect of either combination on cell death at 6 or 24 h. ATO at 50% of the IC50 induced significant cell death at 48 h, while 17 DMAG led to only modest cell death at 50% of the IC50. The inclusion of siRNA to ATO didn’t influence cell death but putting siRNA to 17 DMAG resulted in 50% cell death. The get a handle on siRNA had no influence on cell survival. The inclusion of siRNA to 50% of the IC50 of ATO and 17 DMAG at 48 h did not influence the 50% cell death observed with the mixture. In a previous study, we have shown that HSP90 and ATO inhibitors synergize to inhibit PSTAT3 and increase Metastatic carcinoma their anti leukemia exercise. This synergy occurred despite a synergistic up regulation of HSP70, a protein known to inhibit apoptosis. Pharmacodynamic models were thus applied in our study to study the effect of ATO and 17 DMAG to the down regulation of P STAT3 while inhibiting HSP70 with siRNA. These models not only supported our previous results but also proved the level of synergistic interaction between both agents for your down regulation of P STAT3 increased in siRNA treated AML cells. More over, the synergy that was seen in the up regulation of HSP70 reduced in the presence of siRNA. Exactly the same partial mechanistic pharmacodynamic model was used as in our previous work. The amount of synergy was determined with the estimation of the interaction parameter,. The IC50 values for down regulation contact us of G STAT3 for both agents reduced in the siRNA treated cells, and the SC50 values for the up regulation of HSP70 for both agents increased within the siRNA treated AML cells. The reduction in IC50 values due to the treatment doesn’t show that the level of synergy could also increase using the combination of drugs. An increase in the IC50 value is simply indicative of a development of the potency of drugs. Similarly, an increase in the values due to a treatment is simply indicative of a decrease in potency of the drugs. Two drugs may possibly show a rise in the amount of synergy despite a loss of strength. Greco et al. showed that despite a decline in the efficiency of Trimetrexate and AG2034 in the presence of 78 uM folic acid, there is an increase in the degree of synergy for the two drugs.

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