title: Silencing Bag-1 gene via magnetic gold nanoparticle-delivered siRNA plasmid for colorectal cancer therapy in vivo and in vitro.
abstract: Apoptosis disorder is generally regarded as an important mechanism of carcinogenesis. Inducement of tumor cell apoptosis can be an effectual way to treat cancer. Bcl-2-associated athanogene 1 (Bag-1) is a positive regulator of Bcl-2 which is an anti-apoptotic gene. Bag-1 is highly expressed in colorectal cancer, which plays a critical role in promoting metastasis, poor prognosis, especially in anti-apoptotic function, and is perhaps a valuable gene target for colorectal cancer therapy. Recently, we applied a novel non-viral gene carrier, magnetic gold nanoparticle, and mediated plasmid pGPH1/GFP/Neo-Bag-1-homo-825 silencing Bag-1 gene for treating colorectal cancer in vivo and in vitro. By mediating with magnetic gold nanoparticle, siRNA plasmid was successfully transfected into cell. In 3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide (MTT) assay, magnetic gold nanoparticle had no significant cytotoxicity and by which delivered RNA plasmid inhibited cell viability significantly (P < 0.05). Downregulation of Bag-1 promoted cell apoptosis (∼47.0 %) in vitro and significantly decreased tumor growth when the cells were injected into nude mice. Based on the studies in vivo, the relative expression of Bag-1 was 0.165 ± 0.072 at mRNA level and ∼60 % at protein level. In further study, C-myc and β-catenin, mainly molecules of Wnt/β-catenin pathway, were decreased notably when Bag-1 were silenced in nanoparticle plasmid complex-transfected Balb c/nude tumor xenograft. In conclusion, Bag-1 is confirmed an anti-apoptosis gene that functioned in colorectal cancer, and the mechanism of Bag-1 gene causing colorectal cancer may be related to Wnt/β-catenin signaling pathway abnormality and suggested that magnetic gold nanoparticle-delivered siRNA plasmid silencing Bag-1 is an effective gene therapy method for colorectal cancer.
authors: Department of General Surgery, Qilu Hospital of Shandong University, No. 107 West Wenhua Road, Jinan, Shandong, 200012, People's Republic of China.|School of Medicine, Shandong University, No. 44 West Wenhua Road, Jinan, Shandong, 200012, People's Republic of China.
authors: Wenbai
authors: W
authors: Huang
authors: Department of General Surgery, Qilu Hospital of Shandong University, No. 107 West Wenhua Road, Jinan, Shandong, 200012, People's Republic of China.|School of Medicine, Shandong University, No. 44 West Wenhua Road, Jinan, Shandong, 200012, People's Republic of China.
authors: Zhan'ao
authors: Z
authors: Liu
authors: Department of General Surgery, Qilu Hospital of Shandong University, No. 107 West Wenhua Road, Jinan, Shandong, 200012, People's Republic of China.|School of Medicine, Shandong University, No. 44 West Wenhua Road, Jinan, Shandong, 200012, People's Republic of China.
authors: Guanzhou
authors: G
authors: Zhou
authors: Department of General Surgery, Qilu Hospital of Shandong University, No. 107 West Wenhua Road, Jinan, Shandong, 200012, People's Republic of China.|School of Medicine, Shandong University, No. 44 West Wenhua Road, Jinan, Shandong, 200012, People's Republic of China.
authors: Jianmin
authors: J
authors: Ling
authors: Department of General Surgery, Qilu Hospital of Shandong University, No. 107 West Wenhua Road, Jinan, Shandong, 200012, People's Republic of China.
authors: Ailing
authors: A
authors: Tian
authors: Department of General Surgery, Qilu Hospital of Shandong University, No. 107 West Wenhua Road, Jinan, Shandong, 200012, People's Republic of China. nianfengsun@126.com.
authors: Nianfeng
authors: N
authors: Sun
mesh_terms: D000818:Animals; D015153:Blotting, Western; D045744:Cell Line, Tumor; D015179:Colorectal Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D004268:DNA-Binding Proteins / Q000037:antagonists & inhibitors*; D055785:Gene Knockdown Techniques / Q000379:methods*; D015316:Genetic Therapy / Q000379:methods*; D005822:Genetic Vectors; D006046:Gold; D006801:Humans; D066298:In Vitro Techniques; D008297:Male; D053768:Metal Nanoparticles; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D034741:RNA, Small Interfering; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014157:Transcription Factors / Q000037:antagonists & inhibitors*; D014162:Transfection; D060449:Wnt Signaling Pathway / Q000502:physiology
chemical_list: C091732:BCL2-associated athanogene 1 protein; D004268:DNA-Binding Proteins; D034741:RNA, Small Interfering; D014157:Transcription Factors; D006046:Gold
keywords: Bag-1 gene; Balb c/nude tumor xenograft; Colorectal cancer; Magnetic gold nanoparticles; Small interfering RNA