J Korean Med Sci.  2012 Sep;27(9):987-992. 10.3346/jkms.2012.27.9.987.

Prostaglandin E2 and Interleukin-1beta Reduce E-cadherin Expression by Enhancing Snail Expression in Gastric Cancer Cells

• Jee YS
• Jang TJ
• Jung KH

• KMID: 1782129
• DOI: http://doi.org/10.3346/jkms.2012.27.9.987

Abstract

Inflammation is closely related to the progression of cancer as well as tumorigenesis. Here, we investigated the effect of prostaglandin E2 (PGE2) and interleukin-1beta (IL-1beta) on E-cadherin expression in SNU719 gastric cancer cells. E-cadherin expression decreased as the dose or exposure time of PGE2 and IL-1beta increased, whereas Snail expression increased with dose or time of PGE2 and IL-1beta. E-cadherin expression reduced by PGE2 treatment increased after the transfection of Snail siRNA. Neutralization of IL-1beta using anti-IL-1beta antibody blocked the expression pattern of E-cadherin and Snail occurred by IL-1beta treatment. However, there was no synergic effect of IL-1beta and PGE2 on the expression pattern of E-cadherin and Snail. In conclusion, inflammatory mediators reduced E-cadherin expression by enhancing Snail expression in gastric cancer cells. Inflammation-induced transcriptional regulation of E-cadherin in gastric cancer has implications for targeted chemoprevention and therapy.

Keyword

Gastric cancer; Prostaglandin E2; Interleukin-1beta; E-cadherin; Snail

MeSH Terms

Antibodies/immunology
Antineoplastic Agents/pharmacology
Cadherins/*metabolism
Cell Line, Tumor
Dinoprostone/*pharmacology
Gene Expression Regulation/*drug effects
Humans
Interleukin-1beta/immunology/*pharmacology
RNA Interference
RNA, Small Interfering/metabolism
Stomach Neoplasms/metabolism/pathology
Transcription Factors/antagonists & inhibitors/genetics/*metabolism
Antibodies
Antineoplastic Agents
Cadherins
Interleukin-1beta
RNA, Small Interfering
Transcription Factors
Dinoprostone

Figure

• 

  Fig. 1 Western blot analyses of E-cadherin, COX-2 and Snail in SNU719 and SNU668 cells. (A) Endogenous expression of E-cadherin, COX-2 and Snail in SNU719 and SNU668 cells. (B) Expression of E-cadherin after ectopic expression of Snail in SNU719 cells. Twenty µg of protein was separated by 10% SDS-polyacrylamide gel electrophoresis and transferred to a nitrocellulose membrane. The bottom represents GAPDH, which was used as a loading control.

• 

  Fig. 2 Western blot analyses of E-cadherin and Snail in SNU719 cells treated with PGE2. (A, B) E-cadherin expression decreases as the dose or exposure time of PGE2 increased, whereas Snail expression increases with dose or time of PGE2. Twenty µg of protein was separated by 10% SDS-polyacrylamide gel electrophoresis and transferred to a nitrocellulose membrane. The bottom represents GAPDH, which was used as a loading control.

• 

  Fig. 3 Western blot analyses of E-cadherin in SNU719 cells treated with PGE2 after the transfection of Snail siRNA. Snail siRNA blocks the expression pattern of E-cadherin induced by PGE2 treatment. Twenty µg of protein was separated by 10% SDS-polyacrylamide gel electrophoresis and transferred to a nitrocellulose membrane. The bottom represents GAPDH, which was used as a loading control.

• 

  Fig. 4 Western blot analyses of E-cadherin and Snail in SNU719 cells treated with IL-1β. (A, B) E-cadherin expression decreases as the dose or exposure time of IL-1β increased, whereas Snail expression increased with dose or time of IL-1β. Twenty µg of protein was separated by 10% SDS-polyacrylamide gel electrophoresis and transferred to a nitrocellulose membrane. The bottom represents GAPDH, which was used as a loading control.

• 

  Fig. 5 Western blot analyses of E-cadherin and Snail in SNU719 cells treated with IL-1β after neutralization using anti-IL-1β antibody. Neutralization of IL-1β blocks the expression pattern of E-cadherin and Snail induced by IL-1β treatment. Twenty µg of protein was separated by 10% SDS-polyacrylamide gel electrophoresis and transferred to a nitrocellulose membrane. The bottom represents GAPDH, which was used as a loading control.

• 

  Fig. 6 Western blot analyses of E-cadherin and Snail in SNU719 cells treated with both PGE2 and IL-1β. There is no synergic effect of IL-1β and PGE2 on the expression pattern of E-cadherin and Snail. Twenty µg of protein was separated by 10% SDS-polyacrylamide gel electrophoresis and transferred to a nitrocellulose membrane. The bottom represents GAPDH, which was used as a loading control.

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