Chloroquine enhanced the anticancer capacity of VNP20009 by inhibiting autophagy
Xiaoxin Zhang1, Qiaoqiao Xu1, Zhuangzhuang Zhang1
1The State Key Laboratory of Pharmaceutical Biotechnology, School of Life Science and School of Stomatology, Affiliated Stomatological Hospital, Nanjing University, Nanjing, 210093, Jiangsu, China.
Abstract:
Bacteria-based living anticancer agents have emerged as promising therapeutics. However, the functional role of autophagy in bacterial cancer therapy has been little investigated. In this study, Salmonella VNP20009 induced autophagy in B16F10 cells, which is an unfavorable factor in bacterial cancer therapy. Inhibiting the induction of autophagy by chloroquine or siRNA in bacterial cancer therapy dose- and time-dependently promoted cell death. The combined therapy of VNP20009 and chloroquine not only enhanced the bacterial tumor targeting ability but also facilitated the infiltration of immune cells into the tumor. Our results showed that the combined therapy of VNP20009 and chloroquine could significantly inhibit tumor growth and prolong mouse survival time. This study provides a novel strategy for improving the anti-cancer efficacy of bacterial cancer therapy.
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