Quercetin suppresses cellular migration and invasion in human head and neck squamous cell carcinoma (HNSCC).
Quercetin suppresses cellular migration and invasion in human head and neck squamous cell carcinoma (HNSCC).
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DOI：
10.7603/s40681-016-0015-3
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发表时间：
2016-06
期刊：
影响因子：
--
通讯作者：
Huang CY
中科院分区：
文献类型：
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作者：
Chan CY;Lien CH;Lee MF;Huang CY
表皮生长因子受体 (EGFR) 信号异常的头颈鳞状细胞癌 (HNSCC) 通常与不良预后和低生存率相关。因此，有效抑制 EGFR 信号介导的恶性肿瘤将提高生存率。在之前的一项研究中，我们证明槲皮素通过抑制口腔癌中的 EGFR/Akt 通路，似乎是一种有效的抗肿瘤药物，但其在 HNSCC 中的抗转移潜力仍不清楚 [1]。在这里，我们假设槲皮素可能有效抑制 EGFR 过表达的 HNSCC 细胞的转移。 10 μM（IC50 的半浓度）槲皮素处理可抑制 EGFR 过表达 HSC-3 和 FaDu HNSCC 细胞的细胞迁移和侵袭。槲皮素还抑制嵌入基质胶基质中的 HSC-3 细胞的集落生长。在基质金属蛋白酶（MMP）中，分泌型明胶酶MMP-2和MMP-9负责降解细胞外基质中的明胶和基底膜中的IV型胶原；这种降解事件对于 HNSCC 中从起源迁移到骨的侵袭至关重要。槲皮素 (10 μM) 处理还抑制 MMP-2 和 MMP-9 的表达和蛋白水解活性。综上所述，我们的数据表明槲皮素是一种有效的抗癌剂，可有效对抗 EGFR 过表达 HNSCC 中 MMP-2 和 MMP-9 介导的转移。
Head and neck squamous cell carcinoma (HNSCC) with aberrant epidermal growth factor receptor (EGFR) signaling is often associated with a poor prognosis and a low survival rate. Hence, efficient inhibition of the EGFR signaling-mediated malignancy would improve survival rate. In a previous study, we demonstrated that quercetin appears to be a potent anti-tumorigenic agent through its inhibition of the EGFR/Akt pathway in oral cancer, but its anti-metastatic potential in HNSCC remains unclear [1]. Here, we have hypothesized that quercetin might be effective in metastatic inhibition in EGFR-overexpressing HNSCC cells. Quercetin treatment with 10 μM (half concentration of IC50) suppressed cell migration and invasion in EGFR-overexpressing HSC-3 and FaDu HNSCC cells. Quercetin also inhibited the colony growth of HSC-3 cells embedded in a Matrigel matrix. Among matrix metalloproteinases (MMPs), the secreted gelatinases MMP-2 and MMP-9 are responsible for the degradation of gelatin in the extracellular matrix and type IV collagen in the basement membrane; and this degradation event is crucial for the migration from the origin and the invasion into the bone in HNSCC. Quercetin (10 μM) treatment also suppressed the expression and proteolytic activity of MMP-2 and MMP-9. Taken together, our data indicate that quercetin is an effective anti-cancer agent against MMP-2- and MMP-9-mediated metastasis in EGFR-overexpressing HNSCC.