Dovitinib inhibited the phosphorylation in HT 29 cells which www.selleckchem.com/products/Bicalutamide(Casodex).html decreased further after the combined treatment. SW 480 cells showed a decrease of phosphorylation in all three treatment groups and . Combination of Dovitinib and Oxaliplatin induces DNA damage A very early step in the cellular response to chemothera peutic drugs is DNA double strand breaks followed by the phosphorylation of a histone H2A variant, H2AX, at the site of DNA damage. We determined the extent of DNA damage by adding oxaliplatin and dovitinib. The phosphorylation of H2AX increased in HCT 116 cells after treatment with individual drugs but the combination of two drugs did not show any additional increase. Oxalipla tin or dovitinib alone produced a negligible change in the phosphorylation status in HT 29 and SW 480 cells, how ever, these cells showed a clear increase in phosphorylation with the combination treatment and .

Combination of Dovitinib and Oxaliplatin up regulates expression of pro apoptotic proteins with concomitant decrease in levels of anti apoptotic proteins The pathway leading to induction of apoptosis also in volves p53, where p53 may act in association with other proteins such as Bax and Bcl2 family. We next assayed the expression levels of p53, Bax, Mcl 1, Survivin, Bclxl and Bcl2 in the presence of oxaliplatin and/or dovitinib. Figure 3A shows that treatment of HCT 116, HT 29 and SW 480 cells with the combination of the two drugs for 24 h up regulated the expression of p53 and Bax. However, the expression of Bcl2, Mcl 1, Survivin and Bclxl decreased significantly in all three colon cancer cell lines when treated with the combination of oxaliplatin and dovitinib.

The effect of combination was more pronounced in both proapoptotic and antiapoptotic proteins as compared to either of the drugs alone. The quantitation intensity of each protein band in Figure 3A and with respect to Carfilzomib B actin or tubulin is shown in Figure 3A. Combination of Dovitinib and Oxaliplatin induce apoptosis in colorectal carcinoma cell lines Through quantitative apoptotic cell death assay, we assessed whether the observed synergistic cell growth in hibition by oxaliplatin dovitinib combination is accom panied by greater apoptotic cell death. Figure 3B shows combined population of proapoptotic and apoptotic cell population. http://www.selleckchem.com/products/dorsomorphin-2hcl.html Oxaliplatin and dovitinib individually increased the proapoptotic cell population by 1. 8 fold in HCT 116 cells but the combin ation increased this number to approximately 3fold. HT 29 and SW 480 showed no cell death in the presence of oxaliplatin alone and only marginal increase in annexin positive cells with dovitinib. However, the combination of two drugs increased this number to 1. 6 and 2. 2 fold in HT 29 and SW 480 cell respectively.