Inhibition of β-catenin and STAT3 with a curcumin analog suppresses gastric carcinogenesis in vivo

Yoshihiko Uehara, Masahiro Inoue, Koji Fukuda, Hiroyuki Yamakoshi, Yoshio Hosoi, Hiroaki Kanda, Masanobu Oshima, Yoshiharu Iwabuchi, Hiroyuki Shibata

Research output: Contribution to journalArticlepeer-review

17 Citations (Scopus)

Abstract

Background: Potent chemotherapy for advanced gastric cancer has not been completely established. Many molecularly targeted therapies are under investigation, but their therapeutic outcomes are not promising because they do not target specific and/or critical targets of gastric carcinogenesis. Although the molecular basis of gastric carcinogenesis remains poorly understood, nuclear localization of β-catenin was observed in approximately 50 % of gastric cancer specimens. Recent studies have suggested that activation of signal transducer and activator of transcription 3 (STAT3) contributes to gastric carcinogenesis in a mouse model. A newly synthesized curcumin analog has inhibitory potential against β-catenin and STAT3. Methods: Using a transgenic mouse model of gastric cancer in which β-catenin, cyclooxygenase 2, and microsomal prostaglandin E synthase 1 activation is induced, we examined a curcumin analog with the most enhanced potential for treating gastric cancer through oral administration. Inhibition of these targets was demonstrated using microarray and immunohistochemical analyses. Results: The curcumin analog GO-Y031 decreased the incidence of gastric carcinogenesis to 54.5 % of that of the control (50.0 % vs 91.7 %, p = 0.043), and tumor size was reduced to 51.6 % of that of the control (1.6 mm vs 3.1 mm, p = 0.03). β-Catenin and STAT3 levels were suppressed to 26.2 % (p = 0.00023) and 44.8 % (p = 0.025), respectively, of those of the control. Moreover, macrophage infiltration was suppressed with GO-Y031. Conclusion: β-Catenin and STAT3 can be pharmacologically inhibited in vivo with a curcumin analog, which effectively inhibits β-catenin and STAT3.

Original languageEnglish
Pages (from-to)774-783
Number of pages10
JournalGastric Cancer
Volume18
Issue number4
DOIs
Publication statusPublished - 2015 Oct 25

Keywords

  • Analog
  • Curcumin
  • Gastric cancer
  • Signal transducer and activator of transcription 3
  • β-Catenin

ASJC Scopus subject areas

  • Oncology
  • Gastroenterology
  • Cancer Research

Fingerprint Dive into the research topics of 'Inhibition of β-catenin and STAT3 with a curcumin analog suppresses gastric carcinogenesis in vivo'. Together they form a unique fingerprint.

Cite this