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Lipoxin A4 Attenuates Cell Invasion by Inhibiting ROS/ERK/MMP Pathway in Pancreatic Cancer.

Zong L, Li J, Chen X, Chen K, Li W, Li X, Zhang L, Duan W, Lei J, Xu Q, Shan T, Ma Q, Sun H - Oxid Med Cell Longev (2015)

Bottom Line: Our data showed that LXA4 significantly inhibited both cell invasion and the expression of matrix metalloproteinase- (MMP-) 9 and MMP-2.Further experiments implied that LXA4 decreased the levels of intracellular reactive oxygen species (ROS) and the activity of the extracellular signal regulated kinases (ERK) pathway to achieve similar outcome to ROS scavenger N-acetyl-L-cysteine (NAC).However, a decreased level of intracellular ROS was not observed in cells treated with the specific ERK pathway inhibitor FR180204.

View Article: PubMed Central - PubMed

Affiliation: Department of Hepatobiliary Surgery, First Affiliated Hospital, Xi'an Jiaotong University, Xi'an 710061, China.

ABSTRACT
Lipoxin A4 (LXA4), an endogenous arachidonic acid metabolite, was previously considered an anti-inflammatory lipid mediator. But it also has the potential to inhibit cancer progression. To explore the therapeutic effect of LXA4 in pancreatic cancer, we used Panc-1 cells to investigate the mechanism by which LXA4 can attenuate pancreatic cancer cell invasion. Our data showed that LXA4 significantly inhibited both cell invasion and the expression of matrix metalloproteinase- (MMP-) 9 and MMP-2. Further experiments implied that LXA4 decreased the levels of intracellular reactive oxygen species (ROS) and the activity of the extracellular signal regulated kinases (ERK) pathway to achieve similar outcome to ROS scavenger N-acetyl-L-cysteine (NAC). However, a decreased level of intracellular ROS was not observed in cells treated with the specific ERK pathway inhibitor FR180204. The blocking of either intracellular ROS or ERK pathway caused the downregulation of MMP-9 and MMP-2 expression. Furthermore, tests revealed that LXA4 inhibited MMP-9 and MMP-2 at the mRNA, protein, and functional levels. Finally, LXA4 dramatically limited the invasion of CoCl2-mimic hypoxic cells and abrogated intracellular ROS levels, ERK activity, and MMPs expression. These results suggest that LXA4 attenuates cell invasion in pancreatic cancer by suppressing the ROS/ERK/MMPs pathway, which may be beneficial for preventing the invasion of pancreatic cancer.

No MeSH data available.


Related in: MedlinePlus

LXA4 inhibited cell invasion and decreased expression of MMP-9 and MMP-2. (a) Effect of LXA4 on cell invasion in Panc-1 cells. Cells were treated with either vehicle (methanol) or LXA4 (400 nM) and incubated for 24 hours. Then 1 × 105 cells were transferred into transwell chambers covered with Matrigel. Cultured for 48 hours, cells were stained with 0.1% crystal violet and finally observed and counted under microscope. (b) The quantified results of (a). (c) Representative western blot analysis of MMP-9 and MMP-2 in cells treated like above.  ∗P < 0.05 versus vehicle control.
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fig1: LXA4 inhibited cell invasion and decreased expression of MMP-9 and MMP-2. (a) Effect of LXA4 on cell invasion in Panc-1 cells. Cells were treated with either vehicle (methanol) or LXA4 (400 nM) and incubated for 24 hours. Then 1 × 105 cells were transferred into transwell chambers covered with Matrigel. Cultured for 48 hours, cells were stained with 0.1% crystal violet and finally observed and counted under microscope. (b) The quantified results of (a). (c) Representative western blot analysis of MMP-9 and MMP-2 in cells treated like above.  ∗P < 0.05 versus vehicle control.

Mentions: To test the influence of LXA4 on pancreatic cancer in vitro, we chose the pancreatic cell line Panc-1, which was treated with either the vehicle control (methanol) or 400 nM LXA4 for 24 hours. Then, to test the invasive capability of the treated cells, a transwell assay was performed, which showed that 130.6 ± 9.7 cells in the vehicle control group passed through the Matrigel, whereas 80.2 ± 8.5 cells in the LXA4 group passed through the Matrigel (Figures 1(a) and 1(b)). This suggests that LXA4 could significantly suppress cell invasion. MMP-9 and MMP-2 are two widely accepted proteinases that facilitate cell invasion and metastasis. We also observed that compared with the vehicle control lower levels of MMP-9 and MMP-2 were expressed in Panc-1 cells after they were treated with LXA4 (Figure 1(c)).


Lipoxin A4 Attenuates Cell Invasion by Inhibiting ROS/ERK/MMP Pathway in Pancreatic Cancer.

Zong L, Li J, Chen X, Chen K, Li W, Li X, Zhang L, Duan W, Lei J, Xu Q, Shan T, Ma Q, Sun H - Oxid Med Cell Longev (2015)

LXA4 inhibited cell invasion and decreased expression of MMP-9 and MMP-2. (a) Effect of LXA4 on cell invasion in Panc-1 cells. Cells were treated with either vehicle (methanol) or LXA4 (400 nM) and incubated for 24 hours. Then 1 × 105 cells were transferred into transwell chambers covered with Matrigel. Cultured for 48 hours, cells were stained with 0.1% crystal violet and finally observed and counted under microscope. (b) The quantified results of (a). (c) Representative western blot analysis of MMP-9 and MMP-2 in cells treated like above.  ∗P < 0.05 versus vehicle control.
© Copyright Policy - open-access
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC4663743&req=5

fig1: LXA4 inhibited cell invasion and decreased expression of MMP-9 and MMP-2. (a) Effect of LXA4 on cell invasion in Panc-1 cells. Cells were treated with either vehicle (methanol) or LXA4 (400 nM) and incubated for 24 hours. Then 1 × 105 cells were transferred into transwell chambers covered with Matrigel. Cultured for 48 hours, cells were stained with 0.1% crystal violet and finally observed and counted under microscope. (b) The quantified results of (a). (c) Representative western blot analysis of MMP-9 and MMP-2 in cells treated like above.  ∗P < 0.05 versus vehicle control.
Mentions: To test the influence of LXA4 on pancreatic cancer in vitro, we chose the pancreatic cell line Panc-1, which was treated with either the vehicle control (methanol) or 400 nM LXA4 for 24 hours. Then, to test the invasive capability of the treated cells, a transwell assay was performed, which showed that 130.6 ± 9.7 cells in the vehicle control group passed through the Matrigel, whereas 80.2 ± 8.5 cells in the LXA4 group passed through the Matrigel (Figures 1(a) and 1(b)). This suggests that LXA4 could significantly suppress cell invasion. MMP-9 and MMP-2 are two widely accepted proteinases that facilitate cell invasion and metastasis. We also observed that compared with the vehicle control lower levels of MMP-9 and MMP-2 were expressed in Panc-1 cells after they were treated with LXA4 (Figure 1(c)).

Bottom Line: Our data showed that LXA4 significantly inhibited both cell invasion and the expression of matrix metalloproteinase- (MMP-) 9 and MMP-2.Further experiments implied that LXA4 decreased the levels of intracellular reactive oxygen species (ROS) and the activity of the extracellular signal regulated kinases (ERK) pathway to achieve similar outcome to ROS scavenger N-acetyl-L-cysteine (NAC).However, a decreased level of intracellular ROS was not observed in cells treated with the specific ERK pathway inhibitor FR180204.

View Article: PubMed Central - PubMed

Affiliation: Department of Hepatobiliary Surgery, First Affiliated Hospital, Xi'an Jiaotong University, Xi'an 710061, China.

ABSTRACT
Lipoxin A4 (LXA4), an endogenous arachidonic acid metabolite, was previously considered an anti-inflammatory lipid mediator. But it also has the potential to inhibit cancer progression. To explore the therapeutic effect of LXA4 in pancreatic cancer, we used Panc-1 cells to investigate the mechanism by which LXA4 can attenuate pancreatic cancer cell invasion. Our data showed that LXA4 significantly inhibited both cell invasion and the expression of matrix metalloproteinase- (MMP-) 9 and MMP-2. Further experiments implied that LXA4 decreased the levels of intracellular reactive oxygen species (ROS) and the activity of the extracellular signal regulated kinases (ERK) pathway to achieve similar outcome to ROS scavenger N-acetyl-L-cysteine (NAC). However, a decreased level of intracellular ROS was not observed in cells treated with the specific ERK pathway inhibitor FR180204. The blocking of either intracellular ROS or ERK pathway caused the downregulation of MMP-9 and MMP-2 expression. Furthermore, tests revealed that LXA4 inhibited MMP-9 and MMP-2 at the mRNA, protein, and functional levels. Finally, LXA4 dramatically limited the invasion of CoCl2-mimic hypoxic cells and abrogated intracellular ROS levels, ERK activity, and MMPs expression. These results suggest that LXA4 attenuates cell invasion in pancreatic cancer by suppressing the ROS/ERK/MMPs pathway, which may be beneficial for preventing the invasion of pancreatic cancer.

No MeSH data available.


Related in: MedlinePlus