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

被引：71

作者：

Chen, Jianxiang ^{[1
,2
]}

Qiao, Yiting ^{[1
,2
]}

Tang, Bo ^{[3
,4
]}

Chen, Guo ^{[1
,2
]}

Liu, Xiufeng ^{[1
,2
]}

Yang, Bingya ^{[1
,2
]}

Wei, Jing ^{[1
,2
]}

Zhang, Xiangyu ^{[1
,2
]}

Cheng, Xiawei ^{[1
,2
]}

Du, Pan ^{[1
,2
]}

Jiang, Wenhui ^{[1
,2
]}

Hu, Qingang ^{[1
,2
]}

Hua, Zi-Chun ^{[1
,2
,3
,4
]}

机构：

[1] Nanjing Univ, Affiliated Stomatol Hosp, Sch Stomatol, Sch Life Sci, Nanjing 210023, Jiangsu, Peoples R China

[2] Nanjing Univ, Affiliated Stomatol Hosp, Sch Stomatol, Collaborat Innovat Ctr Chem Life Sci, Nanjing 210023, Jiangsu, Peoples R China

[3] Nanjing Univ, Changzhou High Tech Res Inst, Changzhou 213164, Peoples R China

[4] Jiangsu TargetPharma Labs Inc, Changzhou 213164, Peoples R China

来源：

THERANOSTICS | 2017年 / 7卷 / 08期

关键词：

Salmonella-mediated tumor therapy; melanoma; neutrophils; angiogenesis; ATTENUATED SALMONELLA; TYPHIMURIUM A1-R; PANCREATIC-CANCER; IMMUNE-RESPONSES; LUNG-CANCER; CELLS; GROWTH; CHEMOTHERAPY; METASTASIS; THERAPY;

D O I：

10.7150/thno.18816

中图分类号：

R-3 [医学研究方法]; R3 [基础医学];

学科分类号：

1001 ;

摘要：

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.

引用

页码：2250 / 2260

页数：11

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