Acetylcholinesterase overexpression mediated by oncolytic adenovirus exhibited potent anti-tumor effect

Haineng Xu; Zhengxuan Shen; Jing Xiao; Yu Yang; Weidan Huang; Zhiming Zhou; Jiani Shen; Yizhun Zhu; Xin Yuan Liu; Liang Chu

doi:10.1186/1471-2407-14-668

Acetylcholinesterase overexpression mediated by oncolytic adenovirus exhibited potent anti-tumor effect

Haineng Xu, Zhengxuan Shen, Jing Xiao, Yu Yang, Weidan Huang, Zhiming Zhou, Jiani Shen, Yizhun Zhu, Xin Yuan Liu, Liang Chu

Experimental Radiation Oncology

Research output: Contribution to journal › Article › peer-review

23 Scopus citations

Abstract

Background: Acetylcholinesterase (AChE) mainly functions as an efficient terminator for acetylcholine signaling transmission. Here, we reported the effect of AChE on gastric cancer therapy. Methods: The expression of AChE in gastric cancerous tissues and adjacent non-cancerous tissues was examined by immunohistochemistry. Gastric cancer cells were treated with AChE delivered by replication-deficient adenoviral vector (Ad.AChE) or oncolytic adenoviral vector (ZD55-AChE), respectively, followed by measurement of cell viability and apoptosis by MTT assay and apoptosis detection assays. In vivo, the tumor growth of gastric cancer xenografts in mice treated with Ad.AChE or ZD55-AChE (1 × 10⁹ PFU) were measured. In addition, the cell viability of gastric cancer stem cells treated with Ad.AChE or ZD55-AChE were evaluated by MTT assay. Results: A positive correlation was found between higher level of AChE expression in gastric cancer patient samples and longer survival time of the patients. Ad.AChE and ZD55-AChE inhibited gastric cancer cell growth, and low dose of ZD55-AChE induced mitochondrial pathway of apoptosis in cells. ZD55-AChE repressed tumor growth in vivo, and the anti-tumor efficacy is greater than Ad.AChE. Moreover, ZD55-AChE suppressed the growth of gastric cancer stem cells.Conclusion: ZD55-AChE represented potential therapeutic effect for human gastric cancer.

Original language	English (US)
Article number	668
Pages (from-to)	1-11
Number of pages	11
Journal	BMC cancer
Volume	14
Issue number	1
DOIs	https://doi.org/10.1186/1471-2407-14-668
State	Published - Sep 15 2014

Keywords

AChE
Apoptosis
Gastric cancer
Oncolytic adenovirus

ASJC Scopus subject areas

Genetics
Oncology
Cancer Research

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10.1186/1471-2407-14-668

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@article{231873791fe54f9c8eb13982d0371233,

title = "Acetylcholinesterase overexpression mediated by oncolytic adenovirus exhibited potent anti-tumor effect",

abstract = "Background: Acetylcholinesterase (AChE) mainly functions as an efficient terminator for acetylcholine signaling transmission. Here, we reported the effect of AChE on gastric cancer therapy. Methods: The expression of AChE in gastric cancerous tissues and adjacent non-cancerous tissues was examined by immunohistochemistry. Gastric cancer cells were treated with AChE delivered by replication-deficient adenoviral vector (Ad.AChE) or oncolytic adenoviral vector (ZD55-AChE), respectively, followed by measurement of cell viability and apoptosis by MTT assay and apoptosis detection assays. In vivo, the tumor growth of gastric cancer xenografts in mice treated with Ad.AChE or ZD55-AChE (1 × 109 PFU) were measured. In addition, the cell viability of gastric cancer stem cells treated with Ad.AChE or ZD55-AChE were evaluated by MTT assay. Results: A positive correlation was found between higher level of AChE expression in gastric cancer patient samples and longer survival time of the patients. Ad.AChE and ZD55-AChE inhibited gastric cancer cell growth, and low dose of ZD55-AChE induced mitochondrial pathway of apoptosis in cells. ZD55-AChE repressed tumor growth in vivo, and the anti-tumor efficacy is greater than Ad.AChE. Moreover, ZD55-AChE suppressed the growth of gastric cancer stem cells.Conclusion: ZD55-AChE represented potential therapeutic effect for human gastric cancer.",

keywords = "AChE, Apoptosis, Gastric cancer, Oncolytic adenovirus",

author = "Haineng Xu and Zhengxuan Shen and Jing Xiao and Yu Yang and Weidan Huang and Zhiming Zhou and Jiani Shen and Yizhun Zhu and Liu, {Xin Yuan} and Liang Chu",

note = "Funding Information: We thank Oksana Lockridge (Eppley Institute, University of Nebraska Medical Center) for providing the pGS-AChE plasmid, and the staff at Cell Center of Institute of Biochemistry and Cell Biology for technical assistance in flow cytometry. We thank Tiantao Kuang (Zhongshan Hospital, Shanghai) and Jiasheng Mu (Xinhua Hospital, Shanghai) who provided patient samples. This work was supported by grants from National Basic Research Program of China (973 Program) (2010CB529901, 2011CB510104, 2010CB912603), National Natural Science Fund (31301064, 81372453), Natural Science Foundation of Shanghai (13ZR1446300), the Zhejiang Sci-Tech University grant (1204807-Y), the Key Program of Shanghai Committee of Science and Technology in China (No.10431900100) and Young Scientists Program of Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences (2013KIP101). Publisher Copyright: {\textcopyright} 2014 Xu et al.; licensee BioMed Central Ltd.",

year = "2014",

month = sep,

day = "15",

doi = "10.1186/1471-2407-14-668",

language = "English (US)",

volume = "14",

pages = "1--11",

journal = "BMC cancer",

issn = "1471-2407",

publisher = "BioMed Central",

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T1 - Acetylcholinesterase overexpression mediated by oncolytic adenovirus exhibited potent anti-tumor effect

AU - Xu, Haineng

AU - Shen, Zhengxuan

AU - Xiao, Jing

AU - Yang, Yu

AU - Huang, Weidan

AU - Zhou, Zhiming

AU - Shen, Jiani

AU - Zhu, Yizhun

AU - Liu, Xin Yuan

AU - Chu, Liang

N1 - Funding Information: We thank Oksana Lockridge (Eppley Institute, University of Nebraska Medical Center) for providing the pGS-AChE plasmid, and the staff at Cell Center of Institute of Biochemistry and Cell Biology for technical assistance in flow cytometry. We thank Tiantao Kuang (Zhongshan Hospital, Shanghai) and Jiasheng Mu (Xinhua Hospital, Shanghai) who provided patient samples. This work was supported by grants from National Basic Research Program of China (973 Program) (2010CB529901, 2011CB510104, 2010CB912603), National Natural Science Fund (31301064, 81372453), Natural Science Foundation of Shanghai (13ZR1446300), the Zhejiang Sci-Tech University grant (1204807-Y), the Key Program of Shanghai Committee of Science and Technology in China (No.10431900100) and Young Scientists Program of Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences (2013KIP101). Publisher Copyright: © 2014 Xu et al.; licensee BioMed Central Ltd.

PY - 2014/9/15

Y1 - 2014/9/15

N2 - Background: Acetylcholinesterase (AChE) mainly functions as an efficient terminator for acetylcholine signaling transmission. Here, we reported the effect of AChE on gastric cancer therapy. Methods: The expression of AChE in gastric cancerous tissues and adjacent non-cancerous tissues was examined by immunohistochemistry. Gastric cancer cells were treated with AChE delivered by replication-deficient adenoviral vector (Ad.AChE) or oncolytic adenoviral vector (ZD55-AChE), respectively, followed by measurement of cell viability and apoptosis by MTT assay and apoptosis detection assays. In vivo, the tumor growth of gastric cancer xenografts in mice treated with Ad.AChE or ZD55-AChE (1 × 109 PFU) were measured. In addition, the cell viability of gastric cancer stem cells treated with Ad.AChE or ZD55-AChE were evaluated by MTT assay. Results: A positive correlation was found between higher level of AChE expression in gastric cancer patient samples and longer survival time of the patients. Ad.AChE and ZD55-AChE inhibited gastric cancer cell growth, and low dose of ZD55-AChE induced mitochondrial pathway of apoptosis in cells. ZD55-AChE repressed tumor growth in vivo, and the anti-tumor efficacy is greater than Ad.AChE. Moreover, ZD55-AChE suppressed the growth of gastric cancer stem cells.Conclusion: ZD55-AChE represented potential therapeutic effect for human gastric cancer.

AB - Background: Acetylcholinesterase (AChE) mainly functions as an efficient terminator for acetylcholine signaling transmission. Here, we reported the effect of AChE on gastric cancer therapy. Methods: The expression of AChE in gastric cancerous tissues and adjacent non-cancerous tissues was examined by immunohistochemistry. Gastric cancer cells were treated with AChE delivered by replication-deficient adenoviral vector (Ad.AChE) or oncolytic adenoviral vector (ZD55-AChE), respectively, followed by measurement of cell viability and apoptosis by MTT assay and apoptosis detection assays. In vivo, the tumor growth of gastric cancer xenografts in mice treated with Ad.AChE or ZD55-AChE (1 × 109 PFU) were measured. In addition, the cell viability of gastric cancer stem cells treated with Ad.AChE or ZD55-AChE were evaluated by MTT assay. Results: A positive correlation was found between higher level of AChE expression in gastric cancer patient samples and longer survival time of the patients. Ad.AChE and ZD55-AChE inhibited gastric cancer cell growth, and low dose of ZD55-AChE induced mitochondrial pathway of apoptosis in cells. ZD55-AChE repressed tumor growth in vivo, and the anti-tumor efficacy is greater than Ad.AChE. Moreover, ZD55-AChE suppressed the growth of gastric cancer stem cells.Conclusion: ZD55-AChE represented potential therapeutic effect for human gastric cancer.

KW - AChE

KW - Apoptosis

KW - Gastric cancer

KW - Oncolytic adenovirus

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JF - BMC cancer

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ER -

Acetylcholinesterase overexpression mediated by oncolytic adenovirus exhibited potent anti-tumor effect

Abstract

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