title: Lentivirus-mediated RNA interference targeting Bax inhibitor-1 suppresses ex vivo cell proliferation and in vivo tumor growth of nasopharyngeal carcinoma.
abstract: Bax inhibitor-1 (Bi-1), an anti-apoptotic protein that belongs to the Bcl-2 family, plays an important role in the mitochondrial apoptosis pathway to suppress Bax-induced apoptosis. In several human cancers, including nasopharyngeal carcinoma, its expression was found to be increased; however, up-regulated expression of this protein has been linked to increased cell proliferations. In this study, we down-regulated the gene expression of Bi-1 in nasopharyngeal carcinoma cells by using a lentivirus transfection system packed with short hairpin RNA targeting Bi-1 and used an in vivo model to assess its efficacy as a target in human gene therapy. The data indicated that human malignant nasopharyngeal carcinoma cells, CNE-1 and SUNE-1, transfected with lentiviral short hairpin RNA targeting Bi-1 grew more slowly and showed a higher degree of apoptosis. Moreover, the tumorigenicity of CNE-1 was significantly suppressed when inoculated mice were intratumorically injected with the same vector. Taken together, these data lead us to conclude that Bi-1 plays a crucial role in CNE-1 tumorigenesis and that Bi-1 may be a novel therapeutic target for nasopharyngeal carcinoma.
authors.affiliation: Institute of Biochemistry and Molecular Biology, Guangdong Medical College, Zhanjiang, Guangdong, China.
authors.forename: Xiang-yong
authors.initials: XY
authors.lastname: Li
authors.forename: Yiu-kay
authors.initials: YK
authors.lastname: Lai
authors.forename: Jin-fang
authors.initials: JF
authors.lastname: Zhang
authors.forename: Hai-qing
authors.initials: HQ
authors.lastname: Luo
authors.forename: Mei-hong
authors.initials: MH
authors.lastname: Zhang
authors.forename: Ke-yuan
authors.initials: KY
authors.lastname: Zhou
authors.forename: Hsiang-fu
authors.initials: HF
authors.lastname: Kung
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D051017:Apoptosis Regulatory Proteins / Q000235:genetics / Q000378:metabolism*; D015153:Blotting, Western; D002277:Carcinoma; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects*; D053938:DNA Fragmentation / Q000187:drug effects; D017931:DNA Primers / Q000235:genetics; D015316:Genetic Therapy / Q000379:methods*; D005822:Genetic Vectors / Q000008:administration & dosage / Q000235:genetics / Q000494:pharmacology; D006801:Humans; D016086:Lentivirus; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008819:Mice, Nude; D000077274:Nasopharyngeal Carcinoma; D009303:Nasopharyngeal Neoplasms / Q000235:genetics / Q000628:therapy*; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000008:administration & dosage / Q000235:genetics / Q000494:pharmacology*; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D051017:Apoptosis Regulatory Proteins; D017931:DNA Primers; D008565:Membrane Proteins; D034741:RNA, Small Interfering; C484209:TMBIM6 protein, human