Ginkgolide C (GGC), isolated from Ginkbiloba, has been reported to display various pharmacological actions, although, anti-cancer effect of GGC has been poorly understood till now. This study aimed to investigate whether GGC can exhibit anti-neoplastic effects against colon cancer cells and explore underlying mechanism. The Wnt/β-catenin signaling can regulate cell proliferation, survival, metastasis, and migration. Wnt/β-catenin signaling pathway plays important role in colorectal cancer (CRC) and acts as a potential therapeutic target. Abnormal activation of this signaling cascades has been reported in colon CRC. We found that GGC down-regulated Wnt/β-catenin signaling cascade. GGC inhibited the expression of Wnt3a, β-catenin, and β-catenin down-stream signals (Axin-1, p-GSK3β, and β-TrCP). Also, GGC suppressed the expression of Wnt/β-catenin pathway target genes including c-myc, cyclin D1, and survivin. Additionally, GGC induced apoptosis and suppressed cell proliferation, invasion, and migration. GGC down-regulated the expressions of matrix metalloproteinase (MMP)-9 and MMP-2 proteins. Moreover, silencing of β-catenin by small interfering RNA (siRNA) enhanced the GGC-induced apoptosis and inhibitory action of GGC on invasion. Overall, our results indicate that GGC can reduce proliferation and promote apoptosis in colon cancer cells through inhibition of the Wnt/β-catenin signaling pathway. Thus, GGC can serve as a potent therapeutic agent for management of colon cancer as a novel wnt signaling inhibitor.

中文翻译：

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银杏内酯C通过靶向Wnt/β-catenin信号通路促进结直肠癌细胞凋亡并消除转移

银杏内酯 C (GGC)，从Ginkbiloba中分离，据报道显示出各种药理作用，尽管到目前为止，GGC 的抗癌作用还知之甚少。本研究旨在探讨 GGC 是否对结肠癌细胞具有抗肿瘤作用并探索其潜在机制。Wnt/β-连环蛋白信号可以调节细胞增殖、存活、转移和迁移。Wnt/β-catenin 信号通路在结直肠癌 (CRC) 中发挥重要作用，并作为潜在的治疗靶点。已在结肠 CRC 中报告了这种信号级联的异常激活。我们发现 GGC 下调 Wn​​t/β-catenin 信号级联。GGC 抑制 Wnt3a、β-catenin 和 β-catenin 下游信号（Axin-1、p-GSK3β 和 β-TrCP）的表达。此外，GGC 抑制了 Wnt/β-catenin 通路靶基因的表达，包括 c-myc、cyclin D1 和 survivin。此外，GGC 诱导细胞凋亡并抑制细胞增殖、侵袭和迁移。GGC下调基质金属蛋白酶（MMP）-9和MMP-2蛋白的表达。此外，小干扰RNA（siRNA）对β-连环蛋白的沉默增强了GGC诱导的细胞凋亡和GGC对侵袭的抑制作用。总体而言，我们的结果表明，GGC 可以通过抑制 Wnt/β-catenin 信号通路来减少结肠癌细胞的增殖并促进细胞凋亡。因此，GGC 作为一种新型 wnt 信号抑制剂，可作为治疗结肠癌的有效治疗剂。通过小干扰RNA（siRNA）沉默β-连环蛋白增强了GGC诱导的细胞凋亡和GGC对侵袭的抑制作用。总体而言，我们的结果表明，GGC 可以通过抑制 Wnt/β-catenin 信号通路来减少结肠癌细胞的增殖并促进细胞凋亡。因此，GGC 作为一种新型 wnt 信号抑制剂，可作为治疗结肠癌的有效治疗剂。通过小干扰RNA（siRNA）沉默β-连环蛋白增强了GGC诱导的细胞凋亡和GGC对侵袭的抑制作用。总体而言，我们的结果表明，GGC 可以通过抑制 Wnt/β-catenin 信号通路来减少结肠癌细胞的增殖并促进细胞凋亡。因此，GGC 作为一种新型 wnt 信号抑制剂，可作为治疗结肠癌的有效治疗剂。