Limits...
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 attenuated cell invasion via inhibiting ROS pathway. (a) Cell invasion tested by transwell chamber in Panc-1 cells treated with vehicle (methanol), LXA4 (400 nM), or ROS scavenger NAC (20 mM). (b) The quantified results of (a). (c) Intracellular ROS determined in cells treated in (a). Cells incubated with DCF-DA for 20 min were washed with PBS three times and then lysed by RIPA lysis buffer and tested by fluorimetry at 510 nm. It was normalized by total protein.  ∗P < 0.05 versus vehicle control.
© Copyright Policy - open-access
Related In: Results  -  Collection


getmorefigures.php?uid=PMC4663743&req=5

fig2: LXA4 attenuated cell invasion via inhibiting ROS pathway. (a) Cell invasion tested by transwell chamber in Panc-1 cells treated with vehicle (methanol), LXA4 (400 nM), or ROS scavenger NAC (20 mM). (b) The quantified results of (a). (c) Intracellular ROS determined in cells treated in (a). Cells incubated with DCF-DA for 20 min were washed with PBS three times and then lysed by RIPA lysis buffer and tested by fluorimetry at 510 nm. It was normalized by total protein.  ∗P < 0.05 versus vehicle control.

Mentions: It has been reported that elevated intracellular ROS tends to enhance cell invasion [16], whereas LXA4 can decrease intracellular ROS [17–19]. We treated Panc-1 cells with vehicle, LXA4, and ROS scavenger NAC at 20 mM. Then, we performed cell invasion assay, which demonstrated that fewer cells passed through the Matrigel after they were treated with LXA4 and NAC compared with cells that were treated with vehicle (Figures 2(a) and 2(b)). This demonstrated that ROS might be involved in the regulation of cell invasion. At the same time, based on the intracellular ROS levels that were detected in Panc-1 cells that were treated with vehicle, LXA4, and NAC, the data suggest that LXA4, similar to NAC, decreased the amount of intracellular ROS compared with the vehicle control (Figure 2(c)). These data supported the concept that the suppression of ROS pathway by LXA4 was responsible for attenuated cell invasion.


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 attenuated cell invasion via inhibiting ROS pathway. (a) Cell invasion tested by transwell chamber in Panc-1 cells treated with vehicle (methanol), LXA4 (400 nM), or ROS scavenger NAC (20 mM). (b) The quantified results of (a). (c) Intracellular ROS determined in cells treated in (a). Cells incubated with DCF-DA for 20 min were washed with PBS three times and then lysed by RIPA lysis buffer and tested by fluorimetry at 510 nm. It was normalized by total protein.  ∗P < 0.05 versus vehicle control.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

fig2: LXA4 attenuated cell invasion via inhibiting ROS pathway. (a) Cell invasion tested by transwell chamber in Panc-1 cells treated with vehicle (methanol), LXA4 (400 nM), or ROS scavenger NAC (20 mM). (b) The quantified results of (a). (c) Intracellular ROS determined in cells treated in (a). Cells incubated with DCF-DA for 20 min were washed with PBS three times and then lysed by RIPA lysis buffer and tested by fluorimetry at 510 nm. It was normalized by total protein.  ∗P < 0.05 versus vehicle control.
Mentions: It has been reported that elevated intracellular ROS tends to enhance cell invasion [16], whereas LXA4 can decrease intracellular ROS [17–19]. We treated Panc-1 cells with vehicle, LXA4, and ROS scavenger NAC at 20 mM. Then, we performed cell invasion assay, which demonstrated that fewer cells passed through the Matrigel after they were treated with LXA4 and NAC compared with cells that were treated with vehicle (Figures 2(a) and 2(b)). This demonstrated that ROS might be involved in the regulation of cell invasion. At the same time, based on the intracellular ROS levels that were detected in Panc-1 cells that were treated with vehicle, LXA4, and NAC, the data suggest that LXA4, similar to NAC, decreased the amount of intracellular ROS compared with the vehicle control (Figure 2(c)). These data supported the concept that the suppression of ROS pathway by LXA4 was responsible for attenuated cell invasion.

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