Cancer letters · 2011
Targeting Bcl-2 family proteins in adult T-cell leukemia/lymphoma: in vitro and in vivo effects of the novel Bcl-2 family inhibitor ABT-737.
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Ishitsuka Kenji, Kunami Naoko, Katsuya Hiroo, Nogami Rumiko, Ishikawa Chie, Yotsumoto Fusanori, Tanji Hiroe, Mori Naoki, Takeshita Morishige, Miyamoto Shingo, Tamura Kazuo
Аннотация
Adult T-cell leukemia/lymphoma (ATLL) is a peripheral T-cell malignancy caused by human T-lymphotropic virus type I (HTLV-1). ABT-737, a small molecule inhibitor of Bcl-2, Bcl-X(L), and Bcl-w, significantly induced apoptosis in HTLV-1 infected T-cell lines as well as in fresh ATLL cells, and synergistically enhanced the cytotoxicity and apoptosis induced by conventional cytotoxic drugs. Moreover, ABT-737 significantly inhibited the in vivo tumor growth of an ATLL mouse model. These results suggest that the use of an agent targeting anti-apoptotic bcl-2 family proteins, either alone or in combination with other conventional drugs, represents a novel promising approach for ATLL.
Предметные рубрики MeSH
AdultAnimalsAntineoplastic AgentsApoptosisApoptosis Regulatory ProteinsBiphenyl CompoundsBlotting, WesternCell LineCell Line, TumorCell SurvivalDose-Response Relationship, DrugDrug SynergismFemaleHuman T-lymphotropic virus 1HumansImmunohistochemistryJurkat CellsLeukemia-Lymphoma, Adult T-CellMiceMice, SCIDNitrophenolsPiperazinesProto-Oncogene Proteins c-bcl-2SulfonamidesT-LymphocytesTumor BurdenXenograft Model Antitumor Assaysbcl-X Protein