title: Effect of RNAi-induced down regulation of nuclear factor kappa-B p65 on acute monocytic leukemia THP-1 cells in vitro and vivo.
abstract: NF-κB p65 is found constitutively active in acute monocytic leukemia, and has been considered an important factor for poor prognosis. Therefore, develop specifically target p65 inhibitors will be substantial interest. Until now, although several p65 inhibitors are currently in preclinical and clinical development, none of them are targeting. In this study, siRNA targeting p65 was introduced into the acute monocytic leukemia cell line THP-1 and THP-1 xenograft tumors in nude mice, and then, we measured p65 mRNA and protein levels by real-time RT-PCR and Western blotting, and levels of related protein cyclin D1, Bc1-2, and SMRT by Western blotting. We also investigated the cell cycle and apoptosis via FCM, and cell proliferation by Cell Counting Kit-8 assay. We found that p65 siRNA could effectively reduce the p65 mRNA and protein expression, arrest cells in G0/G1 phase, inhibit the proliferation and increase the apoptosis of THP-1 cells, and intratumoral injection of p65 siRNA could suppress tumor growth in nude mice. We also found that when down regulation of p65, the expression of cyclin D1 and Bc1-2 decreased, and the expression of SMRT increased in vitro and vivo. All these findings suggest that NF-κB p65 maybe an attractive candidate for the therapeutic targeting of acute monocytic leukemia.
authors: Department of Pediatrics, The First Affiliated Hospital of Zhengzhou University, and Department of Epidemiology and Biostatistics, School of Public Health, Zhengzhou University, No. 1 Jianshe East Road, Zhengzhou, 450052, Henan, China. meichun123@126.com
authors: Chunmei
authors: C
authors: Wang
authors: Guangyao
authors: G
authors: Sheng
authors: Jie
authors: J
authors: Lu
authors: Lei
authors: L
authors: Xie
authors: Songting
authors: S
authors: Bai
authors: Yingchao
authors: Y
authors: Wang
authors: Yufeng
authors: Y
authors: Liu
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D015536:Down-Regulation / Q000187:drug effects*; D006801:Humans; D007948:Leukemia, Monocytic, Acute / Q000188:drug therapy* / Q000473:pathology; D051379:Mice; D034622:RNA Interference; D012333:RNA, Messenger / Q000032:analysis; D034741:RNA, Small Interfering / Q000494:pharmacology* / Q000627:therapeutic use; D051996:Transcription Factor RelA / Q000032:analysis / Q000235:genetics*; D023041:Xenograft Model Antitumor Assays
chemical_list: C498143:RELA protein, human; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D051996:Transcription Factor RelA