title: Enhanced therapeutic effect of an antiangiogenesis peptide on lung cancer in vivo combined with salmonella VNP20009 carrying a Sox2 shRNA construct.
abstract: HM-3 is a polypeptide inhibiting angiogenesis. Recent reports suggest that the antitumor effect of angiogenesis inhibitors administered alone might be limited. Cancer stem cells can survive the lack of oxygen and nutrients. To achieve better anti-tumor effect, HM-3 was administered in combination with the attenuated Salmonella typhimurium VNP20009 transformed with a shRNA construct against sex determining region Y-box 2 (Sox2).
  
  
  
  Cell invasion assay and soft agar colony formation assay were used to assess the migration and growth capability of A549 cells once Sox2 was knocked down with the shRNA construct. The shRNA construct targeting Sox2 was transformed into VNP20009. After the mouse xenograft model of A549 was established, HM-3 was co-administered with VNP20009 carrying the shRNA construct. The growth of tumor was checked to compare the effectiveness of different therapies. Western blotting assay and immunohistochemistry staining of the tumor tissue were used to measure the levels of proteins associated with the apoptosis pathway.
  
  
  
  Sox2 was necessary for the migration and growth of A549 cells. The expression of Sox2 was down regulated in the tumor tissue of the combined treatment group of HM-3 with VNP20009 carrying the Sox2 shRNA construct. Together with the accumulation of salmonella in tumor and the inhibition of angiogenesis by HM-3, more tumor cells went through cell apoptosis with increased expression of Bax, cleaved Caspase 3 and decreased expression of Bcl2.
  
  
  
  The results suggest the combination of antiangiogenesis agent HM-3 with gene therapy targeting Sox2 delivered by salmonella as a promising strategy for the treatment of lung cancer.
authors.affiliation: The Engineering Research Center of Peptide Drug Discovery and Development, China Pharmaceutical University, 24 Tongjia Xiang, Nanjing, 210009, People's Republic of China.
authors.forename: Changhong
authors.initials: C
authors.lastname: Zhao
authors.affiliation: The Engineering Research Center of Peptide Drug Discovery and Development, China Pharmaceutical University, 24 Tongjia Xiang, Nanjing, 210009, People's Republic of China.
authors.forename: Junjin
authors.initials: J
authors.lastname: He
authors.affiliation: The Engineering Research Center of Peptide Drug Discovery and Development, China Pharmaceutical University, 24 Tongjia Xiang, Nanjing, 210009, People's Republic of China.
authors.forename: Haoran
authors.initials: H
authors.lastname: Cheng
authors.affiliation: The Engineering Research Center of Peptide Drug Discovery and Development, China Pharmaceutical University, 24 Tongjia Xiang, Nanjing, 210009, People's Republic of China.
authors.forename: Zhaohao
authors.initials: Z
authors.lastname: Zhu
authors.affiliation: The Engineering Research Center of Peptide Drug Discovery and Development, China Pharmaceutical University, 24 Tongjia Xiang, Nanjing, 210009, People's Republic of China. 13913925346@126.com.|State Key Laboratory of Natural Medicines, Ministry of Education, China Pharmaceutical University, 24 Tongjia Xiang, Nanjing, 210009, People's Republic of China. 13913925346@126.com.
authors.forename: Hanmei
authors.initials: H
authors.lastname: Xu
mesh_terms: D000072283:A549 Cells; D020533:Angiogenesis Inhibitors / Q000008:administration & dosage* / Q000494:pharmacology; D000818:Animals; D051017:Apoptosis Regulatory Proteins / Q000378:metabolism; D001428:Bacterial Vaccines / Q000008:administration & dosage* / Q000737:chemistry / Q000494:pharmacology; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D003131:Combined Modality Therapy; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D008175:Lung Neoplasms / Q000378:metabolism / Q000628:therapy*; D051379:Mice; D010455:Peptides / Q000008:administration & dosage* / Q000494:pharmacology; D034741:RNA, Small Interfering / Q000008:administration & dosage* / Q000235:genetics; D055748:SOXB1 Transcription Factors / Q000037:antagonists & inhibitors; D023041:Xenograft Model Antitumor Assays
chemical_list: D020533:Angiogenesis Inhibitors; D051017:Apoptosis Regulatory Proteins; D001428:Bacterial Vaccines; D010455:Peptides; D034741:RNA, Small Interfering; C527782:SOX2 protein, human; D055748:SOXB1 Transcription Factors; C465023:VNP 20009
keywords: Antiangiogenesis; Apoptosis; Lung cancer; Salmonella typhimurium; Sox2