期刊
CANCER LETTERS
卷 389, 期 -, 页码 70-77出版社
ELSEVIER IRELAND LTD
DOI: 10.1016/j.canlet.2016.12.010
关键词
TRAIL; Rocaglamide; Apoptosis; c-FLIP; Myeloma; Leukemia
类别
资金
- Beijing Health System High Level Health Technical Personnel Training Plan [2013-2-007]
Multiple myeloma (MM) is an incurable malignancy by the presently known therapies. TRAIL is a promising anticancer agent that virtually not shows any toxicity to normal cells. We have recently carried out clinical trials with a human circularly permuted TRAIL, CPT against MM saw a partial response in approximate 20-30% of patients. In the current study, we investigated the cause of CPT resistance and revealed that the majority of the MM patients express elevated levels of c-FLIP. Knockdown of c-FLIP expression by siRNA alone was sufficient to increase CPT-mediated apoptosis in a CPT-resistant human MM cell line U266. To overcome CPT resistance, we investigated the combination of CPT with Rocaglamides(s) in MM which has been shown to inhibit c-FLIP expression in vitro. We show that Rocaglamide(s) overcomes CPT resistance in U266 in vitro and significant increases in anti-tumor efficacies of CPT in mice xenografted with U266. Similar results were also obtained in mice xenografted with the CPT-resistant human acute T-cell leukemia cell line Molt-4. Our study suggests that the combination of Rocaglamide(s) with CPT may provide a more efficient treatment against myeloma and leukemia. (C) 2016 Elsevier Ireland Ltd. All rights reserved.
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