Chloroquine Inhibition of Autophagy Enhanced the Anticancer Effects of Listeria monocytogenes in Melanoma

文献类型： 外文期刊

第一作者： Yu, Zuhua

作者： Yu, Zuhua;Zhao, Yingying;Ding, Ke;He, Lei;Liao, Chengshui;Li, Jing;Chen, Songbiao;Shang, Ke;Chen, Jian;Yu, Chuan;Zhang, Chunjie;Li, Yinju;Jia, Yanyan;Yu, Zuhua;Zhao, Yingying;Ding, Ke;He, Lei;Liao, Chengshui;Li, Jing;Chen, Songbiao;Shang, Ke;Chen, Jian;Yu, Chuan;Zhang, Chunjie;Li, Yinju;Jia, Yanyan;Yu, Zuhua;Zhao, Yingying;Ding, Ke;He, Lei;Liao, Chengshui;Li, Jing;Chen, Songbiao;Shang, Ke;Chen, Jian;Yu, Chuan;Zhang, Chunjie;Li, Yinju;Jia, Yanyan;Wang, Shaohui

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关键词： Listeria monocytogenes; autophagy; chloroquine; antitumor; melanoma

期刊名称：MICROORGANISMS （ 影响因子：4.5； 五年影响因子：4.8 ）

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年卷期： 2023 年 11 卷 2 期

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收录情况： SCI

摘要： Listeria monocytogenes has been shown to exhibit antitumor effects. However, the mechanism remains unclear. Autophagy is a cellular catabolic process that mediates the degradation of unfolded proteins and damaged organelles in the cytosol, which is a double-edged sword in tumorigenesis and treatment outcome. Tumor cells display lower levels of basal autophagic activity than normal cells. This study examined the role and molecular mechanism of autophagy in the antitumor effects induced by LM, as well as the combined antitumor effect of LM and the autophagy inhibitor chloroquine (CQ). We investigated LM-induced autophagy in B16F10 melanoma cells by real-time PCR, immunofluorescence, Western blotting, and transmission electron microscopy and found that autophagic markers were increased following the infection of tumor cells with LM. The autophagy pathway in B16F10 cells was blocked with the pharmacological autophagy inhibitor chloroquine, which led to a significant increase in intracellular bacterial multiplication in tumor cells. The combination of CQ and LM enhanced LM-mediated cancer cell death and apoptosis compared with LM infection alone. Furthermore, the combination of LM and CQ significantly inhibited tumor growth and prolonged the survival time of mice in vivo, which was associated with the increased colonization and accumulation of LM and induced more cell apoptosis in primary tumors. The data indicated that the inhibition of autophagy by CQ enhanced LM-mediated antitumor activity in vitro and in vivo and provided a novel strategy to improving the anticancer efficacy of bacterial treatment.

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