title: Plasmid-encoding vasostatin inhibited the growth and metastasis of human hepatocellular carcinoma cells.
abstract: The growth and metastasis of solid tumors depends on angiogenesis. Anti-angiogenesis therapy may represent a promising therapeutic option. Vasostatin, the N-terminal domain of calreticulin, is a very potent endogenous inhibitor of angiogenesis and tumor growth. In this study, we attempted to investigate whether plasmid-encoding vasostatin complexed with cationic liposome could suppress the growth and metastasis of hepatocellular carcinoma in vivo and discover its possible mechanism of action. Apoptosis induction of pSecTag2B-vasostatin plasmid on murine endothelial cells (MS1) was examined by flow cytometric analysis in vitro. Nude mice bearing HCCLM3 tumor received pSecTag2B-vasostatin, pSecTag2B-Null, and 0.9 % NaCl solution, respectively. Tumor net weight was measured and survival time was observed. Microvessel density within tumor tissues was determined by CD31 immunohistochemistry. H&E staining of lungs and TUNEL assay of primary tumor tissues were also conducted. The results displayed that pSecTag2B-vasostatin could inhibit the growth and metastasis of hepatocellular carcinoma xenografts and prolong survival time compared with the controls in vivo. Moreover, histologic analysis revealed that pSecTag2B-vasostatin treatment increased apoptosis and inhibited angiogenesis. The present data may be of importance to the further exploration of this new anti-angiogenesis approach in the treatment of hepatocellular cancer.
authors.affiliation: Department of Medical Oncology, Cancer Center, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, 610041, People's Republic of China, 443459664@qq.com.
authors.forename: Xing-Chen
authors.initials: XC
authors.lastname: Peng
authors.forename: Ming
authors.initials: M
authors.lastname: Wang
authors.forename: Xu-Xia
authors.initials: XX
authors.lastname: Chen
authors.forename: Jing
authors.initials: J
authors.lastname: Liu
authors.forename: Gui-Hua
authors.initials: GH
authors.lastname: Xiao
authors.forename: Hong-Li
authors.initials: HL
authors.lastname: Liao
mesh_terms: D000818:Animals; D037282:Calreticulin / Q000235:genetics* / Q000378:metabolism / Q000494:pharmacology; D006528:Carcinoma, Hepatocellular / Q000473:pathology / Q000628:therapy*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D005260:Female; D015316:Genetic Therapy; D005822:Genetic Vectors / Q000008:administration & dosage; D006801:Humans; D008081:Liposomes / Q000008:administration & dosage*; D008113:Liver Neoplasms / Q000473:pathology / Q000628:therapy*; D051379:Mice; D009362:Neoplasm Metastasis; D009374:Neoplasms, Experimental; D010446:Peptide Fragments / Q000235:genetics* / Q000378:metabolism / Q000494:pharmacology; D010957:Plasmids / Q000235:genetics
chemical_list: D037282:Calreticulin; D008081:Liposomes; D010446:Peptide Fragments; C121986:vasostatin