ABSTRACT Cinnamaldehyde (CA) is known to possess anti‐tumor properties, such as inhibiting proliferation and migration. However, the specific role and molecular mechanism of CA in gastric cancer (GC) remain unclear. This study aimed to elucidate its effects on GC cell proliferation, migration, epithelial‐mesenchymal transition (EMT), and drug resistance, and to explore the potential involvement of follistatin‐like 3 (FSTL3) in these processes. The study employed both in vitro and in vivo approaches. In vitro, GC cells were treated with CA to assess its impact on cell proliferation, migration, and EMT. The expression and role of FSTL3 were analyzed. In vivo, the GC xenograft model and intrasplenic injection liver metastasis model were used to confirm the antitumor effects and the ability to resist metastasis of CA. CA treatment significantly downregulated the expression of FSTL3 in GC cells and altered cytoskeleton expression and distribution. Functionally, CA effectively inhibited GC cell proliferation and migration. These antitumor effects were crucially mediated through FSTL3. The in vivo experiments consistently demonstrated that CA suppressed GC tumor growth, invasion, and metastasis by modulating the expression of EMT‐related proteins and TGF‐β/SMAD signaling via FSTL3. This study demonstrates that the antitumor effects of CA on GC are primarily mediated through FSTL3 downregulation. These findings implicate FSTL3 as a promising therapeutic target for treating GC and overcoming drug resistance.
Zeng et al. (Mon,) studied this question.