Department of Organ Anatomy, Tohoku University Graduate School of Medicine, Seiryo 2-1, Aoba, Sendai, Miyagi, 980-8575, Japan.
Department of Immunology, Akita University, Graduate School of Medicine, Hondo 1-1, Akita, Akita, 010-8543, Japan.
J Biochem. 2023 Nov 30;174(6):511-518. doi: 10.1093/jb/mvad066.
Tumor metastasis is one of the worst prognostic features of cancer. Although metastasis is a major cause of cancer-related deaths, an effective treatment has not yet been established. Here, we explore the antitumor effects of GO-Y030, a curcumin analog, via various mechanisms using a mouse model. GO-Y030 treatment of B16-F10 melanoma cells inhibited TGF-β expression and glycolysis. The invasion assay results showed almost complete invasion inhibition following GO-Y030 treatment. Mouse experiments demonstrated that GO-Y030 administration inhibited lung tumor metastasis without affecting vascular endothelial cells. Consistent with this result, GO-Y030 treatment led to the downregulation of MMP2 and VEGFα, inhibiting tumor invasion and metastasis. The silencing of eIF4B, a downstream molecule of S6, attenuated MMP2 expression. Our study demonstrates the novel efficacy of GO-Y030 in inhibiting tumor metastasis by regulating metastasis-associated gene expression via inhibiting dual access, glycolytic and TGF-β pathways.
肿瘤转移是癌症预后最差的特征之一。尽管转移是癌症相关死亡的主要原因，但尚未建立有效的治疗方法。在这里，我们使用小鼠模型通过各种机制探索姜黄素类似物 GO-Y030 的抗肿瘤作用。GO-Y030 处理 B16-F10 黑色素瘤细胞可抑制 TGF-β表达和糖酵解。侵袭实验结果表明，GO-Y030 处理后几乎完全抑制了侵袭。小鼠实验表明，GO-Y030 给药可抑制肺肿瘤转移，而不影响血管内皮细胞。与这一结果一致，GO-Y030 处理导致 MMP2 和 VEGFα 的下调，抑制肿瘤侵袭和转移。S6 的下游分子 eIF4B 的沉默减弱了 MMP2 的表达。我们的研究表明，GO-Y030 通过抑制双通路、糖酵解和 TGF-β 通路调节转移相关基因表达，从而具有抑制肿瘤转移的新功效。
