科研之友
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摘要
Buckground: Adult T-cell lcukeinia/lvinphoma (ATL) is an aggressive Adult T-cell lcukeinia/lvinphoma malignancy of peripheral T-lymphocytes and its prognosis still remains very poor. Materials and Methods: The potential of combining the Bcl2 homology 3 mimetic ABT-737, which blocks Bcl-2, Bck-X-L and Bel-w, with either the proteasome inhibitor bortezomib or histone deacetylase (HDAC) inhibitor suberoylanilide hydroxamic acid (SAHA) to inhibit the growth of human Tlymphotropic virus type-I (HTLV-I) infected T-cell lines and its mechanism was further evaluated, Results: ABT-737 synergistically induced apoptosis when combined with either bortezotnib or SAHA in HTLV-1 infected T-cell lines and fresh AT!, cells. Bortezomib increased the expression of%26apos; Noxa, which subsequently enhanced the :formation of Mc1-1Noxa complexes, resulting in the functional neutralization of Mc1-1, an inducer of resistance to ABT-737. On the other hand. SAHA reduced the expression of survivin, an antiapoptotic molecule that confers drug resistance on ATL cells. Conclusion: The combination of ABT-737 with bortezomib or SAHA is promising for the treatment of ATL.
- 出版日期2014-10
