Theranostics 2017; 7(8):2250-2260. doi:10.7150/thno.18816

Research Paper

Modulation of Salmonella Tumor-Colonization and Intratumoral Anti-angiogenesis by Triptolide and Its Mechanism

Jianxiang Chen1*, Yiting Qiao1*, Bo Tang2, Guo Chen1, Xiufeng Liu1, Bingya Yang1, Jing Wei1, Xiangyu Zhang1, Xiawei Cheng1, Pan Du1, Wenhui Jiang1, Qingang Hu1, Zi-Chun Hua1, 2✉

1. School of Life Sciences and Collaborative Innovation Center of Chemistry for Life Sciences, School of Stomatology, Affiliated Stomatological Hospital, Nanjing University, Nanjing 210023, People's Republic of China;
2. Changzhou High-Tech Research Institute of Nanjing University and Jiangsu TargetPharma Laboratories Inc., Changzhou 213164, P. R. China.
* These authors contributed equally to the work.

Abstract

The weakened tumour colonization of attenuated Salmonella has severely hampered its clinical development. In this study, we investigated whether an anti-inflammation and antiangiogenesis compound triptolide could improve the efficacy of VNP20009, a highly attenuated Salmonella strain, against mice melanoma. By comparing the effects of conventional VNP20009 monotherapy and a combination therapy that uses both triptolide and VNP20009, we found that triptolide significantly improved the tumour colonization of VNP20009 by reducing the number of infiltrated neutrophils in the melanoma, which led to a larger necrotic area in the melanoma. Moreover, the combination therapy suppressed tumour angiogenesis by reducing the expression of VEGF in a synergistic manner, retarding the growth of the melanoma. Our study revealed that triptolide could significantly enhance the antitumour effect of VNP20009 by modulating tumour angiogenesis and the host immune response, providing a new understanding of the strategy to improve Salmonella-mediated tumour therapy.

Keywords: Salmonella-mediated tumor therapy, melanoma, neutrophils, angiogenesis.

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How to cite this article:
Chen J, Qiao Y, Tang B, Chen G, Liu X, Yang B, Wei J, Zhang X, Cheng X, Du P, Jiang W, Hu Q, Hua ZC. Modulation of Salmonella Tumor-Colonization and Intratumoral Anti-angiogenesis by Triptolide and Its Mechanism. Theranostics 2017; 7(8):2250-2260. doi:10.7150/thno.18816. Available from http://www.thno.org/v07p2250.htm