Therefore, we predicted that a small molecule inhibitor of Bcl XL and were Bcl-2 significantly improve the sensitivity of HNSCC cells to NVP-TAE684 ALK inhibitor chemotherapy. To this M Opportunity to study, UM-22A, 22B and UM were 1483 cells for 48 h with ABT 737 alone, cisplatin alone or various doses of a constant ratio Ratio of ABT 737 and cisplatin treatment. M Possible synergy was evaluated by calculating the values of the combination index method of Chou and Talalay, where CI values below 1.0 are indicative of synergy. As shown, beautiful protected CI far below 1.0 in Table 1 IC 50 values of monotherapy ABT 737, cisplatin, etoposide, or A 793 844 observed against HNSCC cell lines UM 22A, 22B, UM, and 1483 cells were plated in 48 well plates seeded t, grown overnight, then used for 48 h with various doses of medicinal treatment.
Zellvitalit were Th evaluated TW-37 877877-35-5 in triplicate by trypan blue exclusion assay and IC 50 values were calculated. all three cell lines with different doses of the combination 737/cisplatin ABT, indicating a strong synergy between these two agents. To determine whether ABT 737 was synergistic effects with other chemotherapeutic agents in HNSCC cells show, we treated cells with various doses of a constant ratio Ratio of ABT 737 and etoposide. Here, too beautiful protected CI were observed well below 1.0, emphasizes the powerful synergy. To the synergies between 737 and ABT either cisplatin or etoposide best term Were treated 22A Unified Messaging and Unified Messaging-22B cells in the annexin V / propidium iodide flow cytometry assessment tests.
The results obtained in these experiments were quantitatively and qualitatively Similar to those obtained in tests trypan blue exclusion and 3 5 2 2Htetrazolium, inner salt assay. The synergy between ABT-737 and standard chemotherapy drugs in the T Tion of HNSCC cells was best in clonogenic survival assays CONFIRMS. UM-22A cells were incubated for 1 h with 0.1% DMSO, ABT 737 alone, cisplatin alone or cisplatin plus ABT 737 treatment. After treatment, the cells were plated in medium without drug, and colonies were after 12 to 15 days hlt gez. The loss of ABT Klonogenit t in cells treated with cisplatin 737 exceeded the combined losses in cells with ABT 737 alone and cisplatin alone were treated, show superadditive T Tion by combining 737/cisplatin ABT. ABT 737 and chemotherapy synergistically induce the activation of the apoptosis signaling.
To determine whether combinations of ABT 737 and chemotherapeutic agents synergistic activation of apoptosis in HNSCC cells induce, we examined the processing / activation of caspase 3 and PARP cleavage, a caspase 3/7 substrate. For these experiments, UM 22A cells were treated for a short time with 10 m concentrations of each agent alone or the combination of ABT 737, and chemotherapy. Relatively little, if any, processing of caspase-3-3 procaspase compound was prepared in untreated cells or cells with DMSO, ABT 737 alone were, cisplatin alone or etoposide alone treated. In Similar way, only small amounts of PARP cleavage were detected after treatment with various drugs. The combination of ABT 737 plus cisplatin or etoposide, ABT 737 and, in consequence of the occurrence of sensitive active caspase 3 and cleavage of PARP. The degree of activation of caspase 3 and PARP cleavage in response to combined treatment far exceeds the sum of these events in cells with ABT 737 alone or chemotherapy alone were treated. For ABT 737 in synergy with chemotherapeutic agents induce apoptosis important signaling pathways in HNSCC