title: Inhibitory effect of biosynthetic nanoscale peptide Melittin on hepatocellular carcinoma, driven by survivin promoter.
abstract: Hepatic resection and orthotopic liver transplantation are the only potentially curative treatments for hepatocellular carcinoma (HCC) but are indicated only in a minority of patients. Biosynthetic nanoscale peptide Melittin (Mel) is postulated to disrupt microbial phospholipid membranes by formation of stable or transient pores. Survivin, a member of the inhibitor of apoptosis family, is transcriptionally upregulated in most malignant tissues but not in normal tissues. It has been reported that the survivin promoter activity is tumor-specific and makes it a good candidate for construction of gene therapy vectors. In the present study, a non-viral vector (pSURV-Mel), encoding Mel gene, was developed to evaluate its anti-tumor effect in HCC cell lines and in vivo in a mouse model of human HCC xenograft tumor. Our results showed that the survivin promoter is specifically activated in tumor cells, and the pSURV-Mel plasmid expressed Mel selectively in tumor cells and also induced cytotoxicity. Moreover, intratumoral Injection of pSURV-Mel significantly suppressed the growth of xenograft tumors. Mechanistically, pSURV-Mel induced cell death by an apoptosis-dependent pathway. All taken together, this study elucidates a relatively safe, highly effective and cancer specific gene therapy strategy for HCC. The mechanisms of non-viral vector-induced cell death which were revealed by this work will shed light on the construction of more powerful vectors for cancer therapy.
authors.forename: Lili
authors.initials: L
authors.lastname: Qu
authors.forename: Min
authors.initials: M
authors.lastname: Jiang
authors.forename: Zhiyang
authors.initials: Z
authors.lastname: Li
authors.forename: Fuxing
authors.initials: F
authors.lastname: Pu
authors.forename: Lailing
authors.initials: L
authors.lastname: Gong
authors.forename: Li
authors.initials: L
authors.lastname: Sun
authors.forename: Rujun
authors.initials: R
authors.lastname: Gong
authors.forename: Guozhong
authors.initials: G
authors.lastname: Ji
authors.forename: Jin
authors.initials: J
authors.lastname: Si
mesh_terms: D000818:Animals; D040761:Biomimetic Materials / Q000627:therapeutic use; D006528:Carcinoma, Hepatocellular / Q000235:genetics* / Q000473:pathology / Q000628:therapy*; D045744:Cell Line, Tumor; D004247:DNA / Q000008:administration & dosage / Q000235:genetics*; D005260:Female; D015316:Genetic Therapy / Q000379:methods*; D006801:Humans; D051034:Inhibitor of Apoptosis Proteins / Q000235:genetics*; D008113:Liver Neoplasms; D008555:Melitten / Q000235:genetics* / Q000627:therapeutic use; D051379:Mice; D008807:Mice, Inbred BALB C; D053758:Nanoparticles / Q000627:therapeutic use; D011401:Promoter Regions, Genetic / Q000235:genetics*; D012097:Repressor Proteins / Q000235:genetics*; D000077022:Survivin; D016896:Treatment Outcome
chemical_list: C117749:Birc5 protein, mouse; D051034:Inhibitor of Apoptosis Proteins; D012097:Repressor Proteins; D000077022:Survivin; D008555:Melitten; D004247:DNA