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野黄芩苷通过抑制 PI3K/Akt/mTOR 信号通路抑制恶性黑素瘤细胞的侵袭潜能和血管生成。

Scutellarin inhibits the invasive potential of malignant melanoma cells through the suppression epithelial-mesenchymal transition and angiogenesis via the PI3K/Akt/mTOR signaling pathway.

机构信息

Department of Integrated Chinese Traditional and Western Medicine, International Medical School, Tianjin Medical University, No. 22 Qixiangtai, Heping District, Tianjin, 300070, China.

Department of Oncology, Shanghai Pulmonary Hospital Affiliated Tongji University, No. 507 Zhengmin, Yangpu District, Shanghai, 200433, China.

出版信息

Eur J Pharmacol. 2019 Sep 5;858:172463. doi: 10.1016/j.ejphar.2019.172463. Epub 2019 Jun 15.

DOI:10.1016/j.ejphar.2019.172463
PMID:31211986
Abstract

Malignant melanoma is the leading cause of death from skin disease, due in large part to its propensity to metastasize. Scutellarin is an active flavone extracted from traditional Chinese herb Erigeron breviscapus (Vant.) Hand. Mazz. Recent studies have reported that scutellarin can be utilized to treat various types of tumors. In this study, we investigated the effects of scutellarin on melanoma cancer cell invasive potential and the molecular mechanisms underlying these effects using A375 melanoma cells lines. The in-vitro antitumor activity of scutellarin was evaluated by CCK-8 assay, wound-healing assay, transwell assays, adhesion assays, and tube formation assays to assess the cell viability, migration, invasion, adhesion, and angiogenesis, respectively. Also, western blotting assay was used to assess the level of PI3K/Akt/mTOR signaling pathway proteins in A375 cells. We found that scutellarin significantly inhibited melanoma cell lines and HUVECs viability in a time- and concentration-dependent manners. Additionally, scutellarin effectively suppressed tumor cell migration, invasion, adhesion through the suppression of EMT and angiogenesis by inhibiting the PI3K/Akt/mTOR signaling pathway. These results indicated that scutellarin could markedly inhibit the invasive potential of melanoma cell lines by suppressing the EMT and angiogenesis through the PI3K/Akt/mTOR signaling pathway. It suggests that scutellarin might be a potential compound in malignant melanoma treatment.

摘要

恶性黑色素瘤是皮肤疾病导致死亡的主要原因,主要是因为它易于转移。野黄芩苷是从传统中药灯盏细辛(Vant。)Hand。Mazz 中提取的一种活性黄酮。最近的研究报道,野黄芩苷可用于治疗各种类型的肿瘤。在这项研究中,我们使用 A375 黑色素瘤细胞系研究了野黄芩苷对黑色素瘤癌细胞侵袭潜力的影响及其作用机制。通过 CCK-8 测定、划痕愈合试验、Transwell 试验、黏附试验和管形成试验分别评估野黄芩苷对细胞活力、迁移、侵袭、黏附和血管生成的体外抗肿瘤活性。此外,Western blot 测定法用于评估 A375 细胞中 PI3K/Akt/mTOR 信号通路蛋白的水平。我们发现,野黄芩苷以时间和浓度依赖性方式显著抑制黑色素瘤细胞系和 HUVECs 的活力。此外,野黄芩苷通过抑制 EMT 和血管生成有效抑制肿瘤细胞迁移、侵袭和黏附,从而抑制 PI3K/Akt/mTOR 信号通路。这些结果表明,野黄芩苷通过抑制 EMT 和血管生成,通过 PI3K/Akt/mTOR 信号通路,可显著抑制黑色素瘤细胞系的侵袭潜力。这表明野黄芩苷可能是治疗恶性黑色素瘤的一种潜在化合物。

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