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

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.

• Authors: Jianxiang Chen, Yiting Qiao, Bo Tang, Guo Chen, Xiufeng Liu, Bingya Yang, Jing Wei, Xiangyu Zhang, Xiawei Cheng, Pan Du, Wenhui Jiang, Qingang Hu, Zi-Chun Hua
• Journal: Theranostics (Theranostics) Vol. 7 Issue 8 Pg. 2250-2260 ( 2017) ISSN: 1838-7640 [Electronic] Australia
• PMID: 28740548 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Diterpenes
• Epoxy Compounds
• Immunosuppressive Agents
• Phenanthrenes
• Vascular Endothelial Growth Factor A
• triptolide

Topics

• Animals
• Biological Therapy (methods)
• Combined Modality Therapy (methods)
• Disease Models, Animal
• Diterpenes (metabolism, pharmacology)
• Epoxy Compounds (metabolism, pharmacology)
• Immunosuppressive Agents (metabolism, pharmacology)
• Melanoma (microbiology, pathology, therapy)
• Mice, Inbred C57BL
• Necrosis
• Neovascularization, Pathologic (drug therapy)
• Neutrophils (immunology)
• Phenanthrenes (metabolism, pharmacology)
• Salmonella (drug effects, growth & development)
• Treatment Outcome
• Vascular Endothelial Growth Factor A (antagonists & inhibitors)