title: Blockage of autophagy pathway enhances Salmonella tumor-targeting.
abstract: Previous studies have shown that strains of Salmonella typhimurium specifically target tumors in mouse models of cancer. In this study, we report that tumor-targeting Salmonella typhimurium A1-R (A1-R) or VNP20009 induced autophagy in human cancer cells, which serves as a defense response. Functionally, by knockdown of essential autophagy genes Atg5 or Beclin1 in bacteria-infected cancer cells, the autophagy pathway was blocked, which led to a significant increase of intracellular bacteria multiplication in cancer cells. Genetic inactivation of the autophagy pathway enhanced A1-R or VNP20009-mediated cancer cell killing by increasing apoptotic activity. We also demonstrate that the combination of pharmacological autophagy inhibitors chloroquine (CQ) or bafilomycin A1 (Baf A1) with tumor-targeting A1-R or VNP20009 significantly enhanced cancer-cell killing compared with Salmonella infection alone. These findings provide a proof-of-concept of combining autophagy inhibitors and tumor-targeting Salmonella to enhance cancer-cell killing.
authors.affiliation: Cancer Institute, Fudan University Shanghai Cancer Center, Collaborative Innovation Center of Cancer Medicine, Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032, China.|Department of Immunology, Shanghai Medical College, Fudan University, Shanghai 200032, China.|Department of Clinical Laboratory, Children's Hospital, Maternal and Child Health Hospital of Guangxi Zhuang Autonomous Region, Nanning 530003, China.
authors.forename: Binghong
authors.initials: B
authors.lastname: Liu
authors.affiliation: Cancer Institute, Fudan University Shanghai Cancer Center, Collaborative Innovation Center of Cancer Medicine, Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032, China.|Department of Immunology, Shanghai Medical College, Fudan University, Shanghai 200032, China.
authors.forename: Yanan
authors.initials: Y
authors.lastname: Jiang
authors.affiliation: Department of General Surgery, Zhongshan Hospital, Fudan University, Shanghai 200032, China.
authors.forename: Tiangeng
authors.initials: T
authors.lastname: Dong
authors.affiliation: Department of Surgery, University of California, San Diego, California 92103, USA.|AntiCancer, Inc., San Diego, California 92111, USA.
authors.forename: Ming
authors.initials: M
authors.lastname: Zhao
authors.affiliation: Cancer Institute, Fudan University Shanghai Cancer Center, Collaborative Innovation Center of Cancer Medicine, Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032, China.|Department of Immunology, Shanghai Medical College, Fudan University, Shanghai 200032, China.
authors.forename: Jianfu
authors.initials: J
authors.lastname: Wu
authors.affiliation: Cancer Institute, Fudan University Shanghai Cancer Center, Collaborative Innovation Center of Cancer Medicine, Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032, China.
authors.forename: Lihui
authors.initials: L
authors.lastname: Li
authors.affiliation: Department of Immunology, Shanghai Medical College, Fudan University, Shanghai 200032, China.
authors.forename: Yiwei
authors.initials: Y
authors.lastname: Chu
authors.affiliation: Department of Clinical Laboratory, Children's Hospital, Maternal and Child Health Hospital of Guangxi Zhuang Autonomous Region, Nanning 530003, China.
authors.forename: Shangyang
authors.initials: S
authors.lastname: She
authors.affiliation: Department of Clinical Laboratory, Huadong Hospital, Shanghai Key Laboratory of Clinical Geriatric Medicine, Research Center on Aging and Medicine, Fudan University, Shanghai 200040, China.
authors.forename: Hu
authors.initials: H
authors.lastname: Zhao
authors.affiliation: Department of Surgery, University of California, San Diego, California 92103, USA.|AntiCancer, Inc., San Diego, California 92111, USA.
authors.forename: Robert M
authors.initials: RM
authors.lastname: Hoffman
authors.affiliation: Cancer Institute, Fudan University Shanghai Cancer Center, Collaborative Innovation Center of Cancer Medicine, Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032, China.
authors.forename: Lijun
authors.initials: L
authors.lastname: Jia
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D001343:Autophagy; D045744:Cell Line, Tumor; D006801:Humans; D009369:Neoplasms / Q000382:microbiology*; D012480:Salmonella Infections; D012486:Salmonella typhimurium
chemical_list: D000970:Antineoplastic Agents
keywords: Salmonella typhimurium A1-R; apoptosis; autophagy; bacteria; cancer