期刊
MOLECULAR THERAPY
卷 17, 期 2, 页码 269-277出版社
CELL PRESS
DOI: 10.1038/mt.2008.266
关键词
-
资金
- National Natural Science Foundation of China [30500437, 30872272]
- 363 program [2006AA02Z158]
Malignant melanoma (MM) is a major public health problem. The development of effective, systemic therapies for MM is highly desired. We showed here that the transferrin receptor (TfR) was a suitable surface marker for targeting of gene therapy in MM and that the hypoxia-inducible factor-1 alpha (HIF-1 alpha) was an attractive therapeutic molecular target in MM. We observed that inhibition of HIF-1 alpha blocked cell proliferation and induced cell apoptosis in vitro. We then showed that a transferrin-polyethylenimine HIF-1 alpha-short-hairpin RNA (Tf-PEI-HIF-1 alpha-shRNA) complex could target MM specifically and efficiently both in vivo and in vitro, exploiting the high expression of the TfR in MM. The systemic delivery of sequence-specific small-interfering RNA (siRNA) against HIF-1 alpha by the Tf-PEI-HIF-1 alpha-shRNA complex dramatically inhibited tumor growth in the A375 MM xenograft model. The underlying concept of transfecting a HIF-1 alpha shRNA expression vector complexed with Tf-PEI to block HIF-1 alpha holds promise as a clinical approach to gene therapy for MM.
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