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

Jianxiang Chen^1*, Yiting Qiao^1*, Bo Tang², Guo Chen¹, Xiufeng Liu¹, Bingya Yang¹, Jing Wei¹, Xiangyu Zhang¹, Xiawei Cheng¹, Pan Du¹, Wenhui Jiang¹, Qingang Hu¹, Zi-Chun Hua^{1, 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.

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Citation:
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 https://www.thno.org/v07p2250.htm

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.