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

Affiliations
  • 1Department of Surgery, Dankook University Hospital, Cheonan, Korea.
  • 2Department of Pathology, Dongguk University College of Medicine, Gyeongju, Korea. taejung@mail.dongguk.ac.kr
  • 3Department of Surgery, Dongguk University College of Medicine, Gyeongju, Korea.

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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