Research Papers:

The genes slyA, STM3120 and htrA are required for the anticancer ability of VNP20009

Xiaoxin Zhang, Qiaoqiao Xu, Lirun Yang, Yueyang Lai, Zhuangzhuang Zhang, Chao Han, Chizhou Jiang, Jiahuang Li, Yixin Shi and Zi-Chun Hua _

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Oncotarget. 2016; 7:81187-81196. https://doi.org/10.18632/oncotarget.13217

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Xiaoxin Zhang1, Qiaoqiao Xu1, Lirun Yang1, Yueyang Lai1, Zhuangzhuang Zhang1, Chao Han1, Chizhou Jiang1, Jiahuang Li1, Yixin Shi2, Zi-Chun Hua1,3,4,5

1The State Key Laboratory of Pharmaceutical Biotechnology, School of Life Science and School of Stomatology, Affiliated Stomatological Hospital, Nanjing University, Nanjing, 210023, Jiangsu, China

2The School of Life Sciences and the Center for Infectious Diseases and Vaccinology at the Biodesign Institute, Arizona State University, Tempe, Arizona, 85287-4501, USA

3Changzhou High-Tech Research Institute of Nanjing University and Jiangsu TargetPharma Laboratories Inc., Changzhou, 213164, Jiangsu, China

4The State Key Lab of Natural Medicines, China Pharmaceutical University, Nanjing 210017, China

5The State Key Laboratory of Bioelectronics, Southeast University, Nanjing 210008, China

Correspondence to:

Zi-Chun Hua, email: [email protected]

Yixin Shi, email: [email protected]

Keywords: VNP20009, cancer, bacteria, tumor-targeting, immune response

Received: April 29, 2016     Accepted: October 14, 2016     Published: November 08, 2016


VNP20009 is a very effective anti-cancer agent and can specifically target tumors and inhibit tumor growth. It was assumed that the tumor targeting ability of VNP20009 correlated to its anticancer capacity. However, our observation contradicted to this assumption. Three VNP20009 mutant strains (ΔslyA, ΔSTM3120 and ΔhtrA) with reduced fitness in normal tissues and unchanged fitness in tumors partially or completely lost their anti-cancer capacities. The genes slyA, STM3120 and htrA were required for survival within macrophages and were indispensable for tumor microenvironment remodeling by VNP20009. The infiltration of immune cells occurred less in the tumors of mice infected with the mutant strains. In addition, the mRNA levels of TNF-α and IL-1β were significantly decreased in the tumors of mice treated with the mutant strains. Our results indicate that the immune responses elicited by bacteria rather than the bacterial titer in tumors play a “decisive” role in VNP20009-mediated bacterial cancer therapy, which provides a novel perspective for the underlying mechanism of bacterial cancer therapy.

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