Etoposide, cisplatin, etoposide, cisplatin, ABT ABT 737 737 A DMSO treated Bcl-2 Bcl XL 1L Mcl Bax Noxa � Bak B actin cisplatin ABT ABT 737 2 737 untreated cisplatin � 4 8 12 24 36 2 4 8 12 24 36 2 4 8 12 24 36 hours Figure 4 Actin Noxa Synergistic up-regulation of proapoptotic Noxa through the combination of ABT 737 in combination with chemotherapy. TO A were not xl880 849217-64-7 treated or 22A cells were incubated for 24 h with 0.1% DMSO, 10 M ABT 737 only 10 M cisplatin alone, 10 M etoposide alone treated ABT 737 + cisplatin, or ABT 737 and etoposide. After treatment, whole cell lysates were prepared and immunoblotted for indicated proteins. Similar results were observed in three independent Ngigen experiments, and repr Illustrated with representative bodies.
B, UM-22B cells were exposed to ABT 737, ABT 737 cisplatin or cisplatin for the indicated number of hours for Noxa subjected to immunoblotting. The results shown are repr Sentative for three independent Independent experiments. 1236, Li et al. so important, was the effect of including cetuximab modestly. Significant improvements in the therapeutic INO-1001 3544-24-9 efficacies and reduced toxicity in HNSCC t of conventional therapies are likely due to the identification of synergistic drug combinations can be achieved. In this report we show that ABT-737, an inhibitor of Bcl XL and Bcl-2, strong synergy with chemotherapeutic agents on the T Tion of HNSCC cells. We have that the proteasome inhibitor bortezomib demonstrated synergistic with cisplatin in HNSCC cells.
Bortezomib treatment went Not many changes Ver Confinement in the cell to survive Lich inhibition of nuclear factor B, a transcription factor 0 20 40 60 80 100 120% of the cell DMSO ABT ABT 737 737 cisplatin cisplatin nonspecific siRNA siRNA Noxa DMSO ABT ABT cisplatin 737 737 cisplatin cisplatin cisplatin DMSO ABT ABT 737 737 � nonspecific siRNA siRNA Noxa Actin picture. 5th The inhibition of regulation with T Tion of Noxa black cht Combining 737/cisplatin ABT. UM-22A cells were seeded in bo t Its 100 mm, grown overnight, then for 24 h with siRNA or nonspecific siRNA Noxa transfected as described in Materials and Methods. The transfected cells were then either left untreated or treated for 24 h with 0.1% DMSO, 10 M ABT 737 only dealt with 10 M cisplatin alone or cisplatin plus ABT 737. After treatment, the cells were harvested and determined by immunoblotting to a level of protein Noxa.
In addition, trypan blue exclusion tests were used to determine the percentage of survival of cells. The data presented repr The average of three independent means sentieren Ngigen experiments and error bars represent SEM P values were determined using ANOVA followed by multiple comparison Tukey test., P 0.01 ABT 737/cisplatin treated cells compared with siRNA against Noxa siRNA transfected nonspecific. 0 20 40 60 80 100 120% survival of the cell DMSO ABT ABT 737 737 Cisplatin Cisplatin 0.05 per non-specific siRNA 1 siRNA Mcl DMSO Figure 6 Effects of Mcl 1 Down-regulation or overexpression of killing by the combination of ABT 737/cisplatin. A, UM-22A cells were seeded in 100 mm plates t attracted over night and then for 24 h with an siRNA transfected or nonspecific siRNA MCL. The cells were then untreated or were for a further 24 h with 0.1% DMSO, 5 M ABT 737 only, 5 M cisplatin alone or treated ABT 737 plus cisplatin. Immunoblotting was used to demonstrate the inhibition of the expression of MCl 1L, and trypan blue exclusion assays were used to determine the percentage of survival of cells. Colum