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Research Article Open Access
Specific tumor cell targeting remains a challenge for cancer gene therapy. One strategy in overcoming this challenge is by using tumorspecific promoters to drive the expression of delivered genes selectively in cancer cells. In this study, we selected 5′-upstream promoters of survivin, high-mobility group protein B2 (HMGB2), cyclooxygenase-2 (cox-2) and alpha-lactalbumin (LALBA), which have been observed to be significantly upregulated in tumors but have a low level of expression in normal tissues. Plasmid DNA coding for the Discosoma sp. red fluorescent protein (DsRed) under control of the selected promoters were constructed. The activities of these promoters in cancer cell line models of breast cancer (MCF-7 and MDA-MB-231), glioblastoma (U-87 MG and C6), and medulloblastoma (DAOY) were assessed by flow cytometry and a microplate-reader assay. The promoter of cox-2 exhibited the highest transfection efficiency and activity among all the tested promoters, suggesting its broad applicability among multiple cancer types. Furthermore, the LALBA promoter showed the highest selectivity for breast cancer and medulloblastoma. These results should provide a framework for the further development of highly specific and active promoters for targeted cancer gene therapy.
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Author(s): Kui Wang, Forrest M Kievit and Miqin Zhang
Tumor-Specific Promoters, Cancer Cell Lines, Cyclooxygenase-2, Non-viral gene delivery vehicles, Pharmaceutical Technology, Biopharmaceutics, Molecular Drug Design