An HDAC inhibitor enhances cancer therapeutic efficiency of RNA polymerase III promoter-driven IDO shRNA

doi:10.1038/cgt.2013.27

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標題:	An HDAC inhibitor enhances cancer therapeutic efficiency of RNA polymerase III promoter-driven IDO shRNA
作者:	Yen, M-C Weng, T-Y Chen, Y-L Lin, C-C Chen, C-Y Wang, C-Y Chao, H-L Chen, C-S Lai, M-D
貢獻者:	老人服務事業管理系
關鍵字:	H1 Promoter Ido Shrna Indoleamine 2,3-Dioxygenase Osu-Hdac42 Rna Polymerase Iii U6 Promoter
日期:	2013-06
上傳時間:	2014-05-26 10:43:05 (UTC+8)
出版者:	Nature Publishing Group
摘要:	Histone deacetylase (HDAC) inhibitors are used in treating certain human malignancies. Our laboratories demonstrated their capability in enhancing antitumor effect of DNA vaccine driven by an RNA polymerase II (RNA pol II) promoter. However, it is unknown whether HDAC inhibitors enhance the therapeutic short hairpin RNA (shRNA) expressed by an RNA polymerase III (RNA pol III) promoter. We investigated whether HDAC inhibitors augmented antitumor effect of indoleamine 2,3 dioxygenase (IDO) shRNA. HDAC inhibitor OSU-HDAC42 and suberoylanilide hydroxamic acid enhanced RNA pol III-driven U6 and H1 promoter activity in three different cell types in vitro: 293, NIH3T3 and dendritic cell line DC2.4. Subcutaneous injection of OSU-HDAC42 enhanced U6 and H1 promoter activity on abdominal skin of mice in vivo. Combination of IDO shRNA and OSU-HDAC42 increased antitumor effect of IDO shRNA in MBT-2 murine bladder tumor model. IDO shRNA induced tumor-infiltrating CD8(+) and CD4(+) T cells, whereas OSU-HDAC42 treatment induced tumor-infiltrating CD4(+) T cells. Combination of OSU-HDAC42 and IDO shRNA further induced tumor-infiltrating natural killer cells and enhanced interferon-gamma in lymphocytes, but suppressed interleukin (IL)-4 expression of lymphocytes. In addition, OSU-HDAC42 treatment did not alter mRNA expression of IL-12 and tumor necrosis factor-alpha. In conclusion, HDAC inhibitor OSU-HDAC42 may serve as adjuvant of the therapeutic shRNA expressed by an RNA pol III promoter.
關聯:	Cancer Gene therapy, v.20 n.6, pp.351-357
顯示於類別:	[高齡福祉養生管理系] 期刊論文

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