Arginine deiminase inhibits pancreatic cancer cell invasion by blocking PI3K-AKT signaling pathway

Jiang Bo Liu; Liang Liang Lei; Yan Hui Yang; Wei Li; Qing Yong Ma; De Chun Liu; San Qiang Li

doi:10.11569/wcjd.v24.i24.3570

Arginine deiminase inhibits pancreatic cancer cell invasion by blocking PI3K-AKT signaling pathway

Jiang Bo Liu
, Liang Liang Lei
, Yan Hui Yang
, Wei Li
, Qing Yong Ma
, De Chun Liu
, San Qiang Li

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

Abstract

AIM To investigate the impact of arginine deiminase (ADI) on the migration and invasion of human pancreatic cancer cells and the possible mechanism involved. METHODS The pancreatic cancer cell lines PANC-1 expressing defective argininosuccinate synthase (ASS) and BxPC-3 expressing ASS protein were chosen for the ADI treatment experiments, and they were cultured in the medium containing ADI (experimental group) or the common medium without ADI (control group). The impact of ADI on the migration and invasion of the two pancreatic cancer cell lines was examined by scratch assay and transwell invasion assay. The mRNA and protein expression of invasionrelated genes in pancreatic cancer cells treated with ADI was detected by real-time quantitative PCR and/or Western blot. The expression of signal transduction proteins and invasionrelated proteins in PANC-1 cell treated with ADI in combination with PI3K signaling inhibitor LY294002 was also analyzed. RESULTS ADI significantly inhibited cell migration and invasion (P < 0.05), down-regulated the mRNA and protein levels of urokinase plasminogen activator, matrix metalloproteinases (MMP)-2, as well as MMP-9, and elevated the levels of tissue inhibitor of metalloproteinase-2 and E-Cadherin (P < 0.05) in ASS deficient pancreatic cancer cell line PANC-1; while there were no obvious changes for ASS-positive pancreatic cancer cell line BxPC-3. ADI reduced the expression levels of p-AKT and p-p65, which are involved in the PI3K/AKT/nuclear factor-kappa B (NF-κB) signaling, in PANC-1 cells, and PI3K inhibitor LY294002 can synergize the effect of ADI on reducing the levels of phosphorylation of the signaling protein and MMP-2. Furthermore, in combination with ADI, LY294002 synergistically inhibited the invasion ability of pancreatic cancer PANC-1 cells (P < 0.05). CONCLUSION ADI inhibits the invasion of pancreatic cancer cells by regulating the expression of invasionrelated genes via blocking the PI3K-AKT signaling pathway.

Original language	English
Pages (from-to)	3570-3579
Number of pages	10
Journal	World Chinese Journal of Digestology
Volume	24
Issue number	24
DOIs	https://doi.org/10.11569/wcjd.v24.i24.3570
State	Published - 28 Aug 2016
Externally published	Yes

Keywords

Arginine deprivation
Argininosuccinate synthase
Invasion and metastasis
PI3K signaling
Pancreatic cancer

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.11569/wcjd.v24.i24.3570

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@article{f21b1075bcc440ea98f6dba01d16b93f,

title = "Arginine deiminase inhibits pancreatic cancer cell invasion by blocking PI3K-AKT signaling pathway",

abstract = "AIM To investigate the impact of arginine deiminase (ADI) on the migration and invasion of human pancreatic cancer cells and the possible mechanism involved. METHODS The pancreatic cancer cell lines PANC-1 expressing defective argininosuccinate synthase (ASS) and BxPC-3 expressing ASS protein were chosen for the ADI treatment experiments, and they were cultured in the medium containing ADI (experimental group) or the common medium without ADI (control group). The impact of ADI on the migration and invasion of the two pancreatic cancer cell lines was examined by scratch assay and transwell invasion assay. The mRNA and protein expression of invasionrelated genes in pancreatic cancer cells treated with ADI was detected by real-time quantitative PCR and/or Western blot. The expression of signal transduction proteins and invasionrelated proteins in PANC-1 cell treated with ADI in combination with PI3K signaling inhibitor LY294002 was also analyzed. RESULTS ADI significantly inhibited cell migration and invasion (P < 0.05), down-regulated the mRNA and protein levels of urokinase plasminogen activator, matrix metalloproteinases (MMP)-2, as well as MMP-9, and elevated the levels of tissue inhibitor of metalloproteinase-2 and E-Cadherin (P < 0.05) in ASS deficient pancreatic cancer cell line PANC-1; while there were no obvious changes for ASS-positive pancreatic cancer cell line BxPC-3. ADI reduced the expression levels of p-AKT and p-p65, which are involved in the PI3K/AKT/nuclear factor-kappa B (NF-κB) signaling, in PANC-1 cells, and PI3K inhibitor LY294002 can synergize the effect of ADI on reducing the levels of phosphorylation of the signaling protein and MMP-2. Furthermore, in combination with ADI, LY294002 synergistically inhibited the invasion ability of pancreatic cancer PANC-1 cells (P < 0.05). CONCLUSION ADI inhibits the invasion of pancreatic cancer cells by regulating the expression of invasionrelated genes via blocking the PI3K-AKT signaling pathway.",

keywords = "Arginine deprivation, Argininosuccinate synthase, Invasion and metastasis, PI3K signaling, Pancreatic cancer",

author = "Liu, \{Jiang Bo\} and Lei, \{Liang Liang\} and Yang, \{Yan Hui\} and Wei Li and Ma, \{Qing Yong\} and Liu, \{De Chun\} and Li, \{San Qiang\}",

year = "2016",

month = aug,

day = "28",

doi = "10.11569/wcjd.v24.i24.3570",

language = "英语",

volume = "24",

pages = "3570--3579",

journal = "World Chinese Journal of Digestology",

issn = "1009-3079",

publisher = "Baishideng Publishing Group Inc",

number = "24",

}

TY - JOUR

T1 - Arginine deiminase inhibits pancreatic cancer cell invasion by blocking PI3K-AKT signaling pathway

AU - Liu, Jiang Bo

AU - Lei, Liang Liang

AU - Yang, Yan Hui

AU - Li, Wei

AU - Ma, Qing Yong

AU - Liu, De Chun

AU - Li, San Qiang

PY - 2016/8/28

Y1 - 2016/8/28

N2 - AIM To investigate the impact of arginine deiminase (ADI) on the migration and invasion of human pancreatic cancer cells and the possible mechanism involved. METHODS The pancreatic cancer cell lines PANC-1 expressing defective argininosuccinate synthase (ASS) and BxPC-3 expressing ASS protein were chosen for the ADI treatment experiments, and they were cultured in the medium containing ADI (experimental group) or the common medium without ADI (control group). The impact of ADI on the migration and invasion of the two pancreatic cancer cell lines was examined by scratch assay and transwell invasion assay. The mRNA and protein expression of invasionrelated genes in pancreatic cancer cells treated with ADI was detected by real-time quantitative PCR and/or Western blot. The expression of signal transduction proteins and invasionrelated proteins in PANC-1 cell treated with ADI in combination with PI3K signaling inhibitor LY294002 was also analyzed. RESULTS ADI significantly inhibited cell migration and invasion (P < 0.05), down-regulated the mRNA and protein levels of urokinase plasminogen activator, matrix metalloproteinases (MMP)-2, as well as MMP-9, and elevated the levels of tissue inhibitor of metalloproteinase-2 and E-Cadherin (P < 0.05) in ASS deficient pancreatic cancer cell line PANC-1; while there were no obvious changes for ASS-positive pancreatic cancer cell line BxPC-3. ADI reduced the expression levels of p-AKT and p-p65, which are involved in the PI3K/AKT/nuclear factor-kappa B (NF-κB) signaling, in PANC-1 cells, and PI3K inhibitor LY294002 can synergize the effect of ADI on reducing the levels of phosphorylation of the signaling protein and MMP-2. Furthermore, in combination with ADI, LY294002 synergistically inhibited the invasion ability of pancreatic cancer PANC-1 cells (P < 0.05). CONCLUSION ADI inhibits the invasion of pancreatic cancer cells by regulating the expression of invasionrelated genes via blocking the PI3K-AKT signaling pathway.

AB - AIM To investigate the impact of arginine deiminase (ADI) on the migration and invasion of human pancreatic cancer cells and the possible mechanism involved. METHODS The pancreatic cancer cell lines PANC-1 expressing defective argininosuccinate synthase (ASS) and BxPC-3 expressing ASS protein were chosen for the ADI treatment experiments, and they were cultured in the medium containing ADI (experimental group) or the common medium without ADI (control group). The impact of ADI on the migration and invasion of the two pancreatic cancer cell lines was examined by scratch assay and transwell invasion assay. The mRNA and protein expression of invasionrelated genes in pancreatic cancer cells treated with ADI was detected by real-time quantitative PCR and/or Western blot. The expression of signal transduction proteins and invasionrelated proteins in PANC-1 cell treated with ADI in combination with PI3K signaling inhibitor LY294002 was also analyzed. RESULTS ADI significantly inhibited cell migration and invasion (P < 0.05), down-regulated the mRNA and protein levels of urokinase plasminogen activator, matrix metalloproteinases (MMP)-2, as well as MMP-9, and elevated the levels of tissue inhibitor of metalloproteinase-2 and E-Cadherin (P < 0.05) in ASS deficient pancreatic cancer cell line PANC-1; while there were no obvious changes for ASS-positive pancreatic cancer cell line BxPC-3. ADI reduced the expression levels of p-AKT and p-p65, which are involved in the PI3K/AKT/nuclear factor-kappa B (NF-κB) signaling, in PANC-1 cells, and PI3K inhibitor LY294002 can synergize the effect of ADI on reducing the levels of phosphorylation of the signaling protein and MMP-2. Furthermore, in combination with ADI, LY294002 synergistically inhibited the invasion ability of pancreatic cancer PANC-1 cells (P < 0.05). CONCLUSION ADI inhibits the invasion of pancreatic cancer cells by regulating the expression of invasionrelated genes via blocking the PI3K-AKT signaling pathway.

KW - Arginine deprivation

KW - Argininosuccinate synthase

KW - Invasion and metastasis

KW - PI3K signaling

KW - Pancreatic cancer

UR - https://www.scopus.com/pages/publications/84984599938

U2 - 10.11569/wcjd.v24.i24.3570

DO - 10.11569/wcjd.v24.i24.3570

M3 - 文章

AN - SCOPUS:84984599938

SN - 1009-3079

VL - 24

SP - 3570

EP - 3579

JO - World Chinese Journal of Digestology

JF - World Chinese Journal of Digestology

IS - 24

ER -

Arginine deiminase inhibits pancreatic cancer cell invasion by blocking PI3K-AKT signaling pathway

Abstract

Keywords

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