gms | German Medical Science

83rd Annual Meeting of the German Society of Oto-Rhino-Laryngology, Head and Neck Surgery

German Society of Oto-Rhino-Laryngology, Head and Neck Surgery

16.05. - 20.05.2012, Mainz

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Antitumor potential of SLPI promoter controlled recombinant caspase-3 expression in laryngeal carcinoma

Meeting Abstract

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  • Jia Chen - The Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, P.R. China
  • Beibei Yang - The Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, P.R. China
  • Shoude Zhang - The Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, P.R. China
  • Jingjia Ye - Clinical Research Center, The Second Affiliated Hospital, School of Medicine, Zh, Hangzhou, P.R. China
  • Zhenyu Jia - Institute of Hygiene, Zhejiang Academy of Medical Sciences, Hangzhou, P.R. China
  • Jiang Cao - Clinical Research Center, The Second Affiliated Hospital, School of Medicine, Zh, Hangzhou, P.R. China

Deutsche Gesellschaft für Hals-Nasen-Ohren-Heilkunde, Kopf- und Hals-Chirurgie. 83. Jahresversammlung der Deutschen Gesellschaft für Hals-Nasen-Ohren-Heilkunde, Kopf- und Hals-Chirurgie. Mainz, 16.-20.05.2012. Düsseldorf: German Medical Science GMS Publishing House; 2012. Doc12hnod212

doi: 10.3205/12hnod212, urn:nbn:de:0183-12hnod2120

Published: April 4, 2012

© 2012 Chen et al.
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Outline

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The purpose of this study is to develop a specific and efficient targeted gene therapy approach for laryngeal carcinomas. Several promoters were cloned and evaluated for transcription regulation potential. One SLPI promoter fragment (-650 to +22) showed the highest efficiency and specificity among the promoters of SCCA2, SLPI（-849 to +22, -531 to +22）and survivin in laryngeal carcinoma Hep-2 cells, and was used for expression control of an active recombinant caspases-3 (revCasp3). Adenoviral vector was constructed (Ad-SLPI-revCasp3), and antitumor efficacy was assessed in vitro and in vivo. RevCasp3 was successfully expressed in Hep-2 cells with efficient activation of endogenous Caspase-3, leading to specific apoptosis of Hep-2 cells when compared to the control normal HuVEC cells. In laryngeal carcinoma xenograft model in nude mice, intratumoral administration of Ad-SLPI-revCasp3 significantly inhibited tumor growth, without any obvious toxicity. In summary, the specific and efficient apoptosis-inducing potential of Ad-SLPI-revCasp3 makes it a new approach of targeted gene therapy for laryngeal squamous cell carcinoma