title: Antitumor potential of SLPI promoter controlled recombinant caspase-3 expression in laryngeal carcinoma.
abstract: The purpose of this study is to develop a specific and efficient targeted gene therapy candidate approach for laryngeal carcinomas. Several promoters of human squamous cell carcinoma antigen 2(SCCA2), secretory leukocyte protease inhibitor (SLPI) and Survivin genes were cloned from human genomic DNA and evaluated for tumor-specific transcription potential in human laryngeal carcinoma Hep-2 cells by dual luciferase assays. One SLPI promoter fragment (677 bp) showed the highest efficiency and specificity, and was used to control the expression of a recombinant active caspases-3 (revCasp3), which could trigger apoptosis without activation of its upstream cascade elements once expressed in a cell, in an adenoviral vector (Ad-SLPI-revCasp3), and its antitumor efficacy was assessed. In vitro infection with Ad-SLPI-revCasp3 showed revCasp3 could be specifically expressed in Hep-2 cells, resulting in efficient activation of endogenous Caspase-3 and subsequent apoptosis of Hep-2 cells. In Hep-2 nude mice xenograft model, intratumoral administration of Ad-SLPI-revCasp3 significantly inhibited tumor growth without obvious loss of body weight and obvious hepatic toxicity. In summary, our study showed the specific and efficient apoptosis-inducing potential of Ad-SLPI-revCasp3, and this makes it a new candidate approach of targeted gene therapy for laryngeal squamous cell carcinoma, which needs further systematic investigation.
authors.affiliation: Department of Otorhinolaryngology, The Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China.
authors.forename: J
authors.initials: J
authors.lastname: Chen
authors.forename: B
authors.initials: B
authors.lastname: Yang
authors.forename: S
authors.initials: S
authors.lastname: Zhang
authors.forename: Y
authors.initials: Y
authors.lastname: Ling
authors.forename: J
authors.initials: J
authors.lastname: Ye
authors.forename: Z
authors.initials: Z
authors.lastname: Jia
authors.forename: J
authors.initials: J
authors.lastname: Cao
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000235:genetics; D002294:Carcinoma, Squamous Cell / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D053148:Caspase 3 / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism; D045744:Cell Line, Tumor; D004195:Disease Models, Animal; D015316:Genetic Therapy / Q000379:methods*; D006801:Humans; D007822:Laryngeal Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology / Q000628:therapy*; D051379:Mice; D008819:Mice, Nude; D011401:Promoter Regions, Genetic; D053481:Secretory Leukocyte Peptidase Inhibitor / Q000235:genetics*; D023041:Xenograft Model Antitumor Assays
chemical_list: C506814:SLPI protein, human; D053481:Secretory Leukocyte Peptidase Inhibitor; D053148:Caspase 3