Enhanced therapeutic effect of an antiangiogenesis peptide on lung cancer in vivo combined with salmonella VNP20009 carrying a Sox2 shRNA constructReport as inadecuate




Enhanced therapeutic effect of an antiangiogenesis peptide on lung cancer in vivo combined with salmonella VNP20009 carrying a Sox2 shRNA construct - Download this document for free, or read online. Document in PDF available to download.

Journal of Experimental and Clinical Cancer Research

, 35:107

First Online: 02 July 2016Received: 29 March 2016Accepted: 21 June 2016DOI: 10.1186-s13046-016-0381-4

Cite this article as: Zhao, C., He, J., Cheng, H. et al. J Exp Clin Cancer Res 2016 35: 107. doi:10.1186-s13046-016-0381-4

Abstract

BackgroundHM-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.

MethodsCell 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.

ResultsSox2 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.

ConclusionsThe 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.

KeywordsSox2 Lung cancer Antiangiogenesis Salmonella typhimurium Apoptosis  Download fulltext PDF



Author: Changhong Zhao - Junjin He - Haoran Cheng - Zhaohao Zhu - Hanmei Xu

Source: https://link.springer.com/







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