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WYC-209 suppresses gastric cancer by down-regulating FGF18 via inactivating the STAT3 signaling pathway

Zhenyuan Qian1, Wenfa Lin2, Xufan Cai2

  • 1General Surgery, Cancer Center, Department of Gastrointestinal and Pancreatic Surgery, Zhejiang Provincial People's Hospital, Affiliated People's Hospital, Hangzhou Medical College, Hangzhou, Zhejiang, China.

European Journal of Pharmacology
|August 30, 2024
PubMed
Abstract

Insights

WYC-209 effectively suppresses gastric cancer (GC) by inhibiting tumor growth and metastasis. This novel compound targets fibroblast growth factor-18 (FGF18) via the STAT3 signaling pathway, offering a promising therapeutic strategy for GC.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cancer Research

Background:

  • Gastric cancer (GC) poses a significant global health challenge.
  • WYC-209 demonstrates inhibitory effects on tumor-repopulating cells (TRCs), but its role in GC is unexamined.
  • This study investigates WYC-209's impact on GC and its underlying molecular mechanisms.

Purpose of the Study:

  • To evaluate the efficacy of WYC-209 in inhibiting gastric cancer cell survival, migration, and invasion.
  • To elucidate the molecular pathways targeted by WYC-209 in gastric cancer.
  • To assess the in vivo therapeutic potential of WYC-209 against gastric cancer.

Main Methods:

  • Cell viability, migration, invasion, and colony formation assays were performed on GC cell lines (AGS, HGC-27).
  • RNA sequencing (RNA-seq) and pathway enrichment analyses identified key molecular targets and pathways.
  • In vivo efficacy was assessed using xenograft models; mechanistic studies included loss/gain-of-function, ChIP, and luciferase reporter assays.

Main Results:

  • WYC-209 significantly inhibited GC cell motility in vitro and tumor growth in vivo.
  • RNA-seq identified fibroblast growth factor-18 (FGF18) as a key target; FGF18 overexpression counteracted WYC-209's effects.
  • WYC-209 inactivated the STAT3 signaling pathway, reducing FGF18 expression by preventing STAT3 binding to the FGF18 promoter.

Conclusions:

  • WYC-209 exhibits significant anti-gastric cancer potential.
  • The compound functions by down-regulating FGF18 expression through the inactivation of the STAT3 signaling pathway.
  • These findings highlight WYC-209 as a promising therapeutic candidate for gastric cancer treatment.
Keywords:
FGF18Gastric cancer (GC)STAT3 signaling pathwaySynthetic retinoidWYC-209

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