Metastasis is the most prevalent cause of cancer-related deaths and treatment failure in patients with hepatocellular carcinoma (HCC). Kaempferol is a natural flavonol belonging to the subgroup of flavonoids and exhibits potent anticancer activities. This study provides molecular evidence on the anti-invasive and anti-migratory effects of kaempferol on human HCC cells. The anti-invasive effect was investigated by applying kaempferol on two human HCC cell lines (Huh-7 and SK-Hep-1). Kaempferol reduced the invasion and migration of Huh-7 and SK-Hep-1 cells by Boyden chamber invasion assay and wound healing assay, respectively. A protease array analysis showed that Matrix Metalloproteinase-9 (MMP-9) was dramatically downregulated in HCC cells after kaempferol treatment. Gelatin zymography and Western blot assay showed that kaempferol reduced the activities and protein expression of MMP-9, respectively. Kaempferol also sufficiently suppressed the phosphorylation of the Akt expression. Overall, kaempferol inhibited the invasive properties of human HCC cells by targeting MMP-9 and Akt pathways. Hence, kaempferol could be used as an adjuvant therapeutic agent for the treatment of human HCC cells.

中文翻译：

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山奈酚通过抑制 MMP-9 和 Akt 信号通路抑制人肝癌细胞的细胞迁移

转移是肝细胞癌 (HCC) 患者癌症相关死亡和治疗失败的最常见原因。Kaempferol 是一种天然黄酮醇，属于类黄酮亚组，具有强大的抗癌活性。本研究提供了关于山奈酚对人类 HCC 细胞的抗侵袭和抗迁移作用的分子证据。通过将山奈酚应用于两种人 HCC 细胞系（Huh-7 和 SK-Hep-1）来研究抗侵袭作用。通过 Boyden 室侵袭试验和伤口愈合试验，山奈酚分别降低了 Huh-7 和 SK-Hep-1 细胞的侵袭和迁移。蛋白酶阵列分析显示基质金属蛋白酶-9 (MMP-9) 在山奈酚处理后在 HCC 细胞中显着下调。明胶酶谱和蛋白质印迹分析表明，山奈酚分别降低了 MMP-9 的活性和蛋白表达。Kaempferol 还充分抑制了 Akt 表达的磷酸化。总体而言，山奈酚通过靶向 MMP-9 和 Akt 通路抑制人类 HCC 细胞的侵袭特性。因此，山柰酚可用作治疗人HCC细胞的辅助治疗剂。