title: Adenovirus siMDM2 and NDRG2 Gene Therapy Inhibits Cell Proliferation and Induces Apoptosis of Squamous Cell Carcinoma.
abstract: Squamous cell carcinoma (SCC) is one of the most common skin cancers. In the present study, we explored the effects of depletion of murine double minute gene 2 (MDM2) together with overexpression of N-myc downstream-regulated gene 2 (NDRG2) on cutaneous SCC. In order to achieve high efficiency of gene knockdown and overexpression in SCC-13 cells, recombinant adenovirus carrying siMDM2 and NDRG2 expression construct was produced. We found Ad-siMDM2, Ad-NDRG2, and Ad-siMDM2-NDRG2 infections inhibit the growth of SCC-13 cells in vitro, and Ad-siMDM2-NDRG2 infection has the highest inhibitory effect. Subcutaneous injections of Ad-siMDM2, Ad-NDRG2, and Ad-siMDM2-NDRG2 into SCC-13 xenograft nude mice resulted in the reduction of tumor volume. Moreover, we found that apoptosis protein caspase 3 was up-regulated in the Ad-siMDM2-, Ad-NDRG2-, and Ad-siMDM2-NDRG2-treated groups. Our data indicate that the adenovirus-mediated MDM2 silencing and NDRG2 overexpression can synergistically inhibit local cancer cell proliferation, induce apoptosis, and further prevent metastases of SCC. Our study provides a promising method that can be further developed as a new therapeutic approach against SCC.
authors.affiliation: Department of Dermatology, Linyi People's Hospital, Linyi, 276003, China.|Department of Dermatology, Shandong Provincial Hospital affiliated to Shandong University, 324# Jingwuweiqi Road, Jinan, 250021, China.
authors.forename: Shouzhong
authors.initials: S
authors.lastname: Wang
authors.affiliation: Department of Dermatology, Shandong Provincial Hospital affiliated to Shandong University, 324# Jingwuweiqi Road, Jinan, 250021, China.
authors.forename: Nan
authors.initials: N
authors.lastname: Chen
authors.affiliation: Department of Dermatology, Linyi People's Hospital, Linyi, 276003, China.
authors.forename: Na
authors.initials: N
authors.lastname: Dong
authors.affiliation: Department of Dermatology, Linyi People's Hospital, Linyi, 276003, China.
authors.forename: Leihong
authors.initials: L
authors.lastname: Lu
authors.affiliation: Department of Dermatology, Linyi People's Hospital, Linyi, 276003, China.
authors.forename: Liqian
authors.initials: L
authors.lastname: Liu
authors.affiliation: Department of Dermatology, Shandong Provincial Hospital affiliated to Shandong University, 324# Jingwuweiqi Road, Jinan, 250021, China. drzhangli02@163.com.
authors.forename: Li
authors.initials: L
authors.lastname: Zhang
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D000256:Adenoviridae / Q000235:genetics; D000818:Animals; D017209:Apoptosis; D015153:Blotting, Western; D002294:Carcinoma, Squamous Cell / Q000378:metabolism / Q000473:pathology / Q000628:therapy*; D053148:Caspase 3 / Q000378:metabolism; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D015316:Genetic Therapy; D051379:Mice; D008819:Mice, Nude; D011506:Proteins / Q000235:genetics* / Q000378:metabolism; D051736:Proto-Oncogene Proteins c-mdm2 / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000378:metabolism*; D060888:Real-Time Polymerase Chain Reaction; D012878:Skin Neoplasms / Q000378:metabolism / Q000473:pathology / Q000628:therapy*; D014162:Transfection; D014183:Transplantation, Heterologous; D015854:Up-Regulation
chemical_list: D048868:Adaptor Proteins, Signal Transducing; C485172:Ndr2 protein, mouse; D011506:Proteins; D034741:RNA, Small Interfering; C497207:Mdm2 protein, mouse; D051736:Proto-Oncogene Proteins c-mdm2; D053148:Caspase 3
keywords: Gene silencing; Gene therapy; Murine double minute 2; N-myc downstream-regulated gene 2; Squamous cell carcinoma