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蒲公英籽提取物影响食管鳞状细胞癌的肿瘤进展并增强顺铂敏感性。

Dandelion Seed Extract Affects Tumor Progression and Enhances the Sensitivity of Cisplatin in Esophageal Squamous Cell Carcinoma.

作者信息

Li Yuxi, Deng Yuying, Zhang Xiuli, Fu Han, Han Xue, Guo Wenqing, Zhao Wei, Zhao Xuening, Yu Chunxue, Li Hui, Lei Kaijian, Wang Tianxiao

机构信息

School of Pharmacy, Henan University, Kaifeng, China.

Department of Botany, Liaoning Agricultural College, Yingkou, China.

出版信息

Front Pharmacol. 2022 May 20;13:897465. doi: 10.3389/fphar.2022.897465. eCollection 2022.

DOI:10.3389/fphar.2022.897465
PMID:35668940
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9164105/
Abstract

Like dandelion, dandelion seed also have anti-inflammatory activity. Therefore, in this article, we intend to explore the anti-cancer availability of aqueous dandelion seed extract (DSE) in esophageal squamous cell carcinoma (ESCC). Firstly, the effects of DSE on cell proliferation, apoptosis, migration, invasion and angiogenesis were investigated. Then to explore the mechanism of DSE against ESCC, the levels of proliferation-associated proteins (PI3K, Akt and pAkt), apoptosis-associated proteins (survivin, Bcl-2, Bax, caspase3 and caspase9), metastasis-associated proteins (MMP2, MMP9, VEGF) and EMT progression-associated proteins (Snail, E-cadherin and Vimentin) were analyzed. Next, we further explored the effect of DSE on the sensitivity of cisplatin (DDP) in ESCC cells and investigated the effect of DSE combined with DDP on DNA damage repair-associated proteins (MSH2, MLH1 and ERCC1) and drug resistant target protein STAT3. The results indicated that DSE selectively inhibited cell growth, proliferation, migration, invasion, angiogenesis and induced cell apoptosis in ESCC cells. It was observed the decreased PI3K, Akt and pAkt proteins levels in KYSE450 and Eca109 cells administrated with DSE. The data also showed that the application of DSE decreased the level of survivin and the ratio of Bcl-2/Bax, while increased the levels of caspase3 and caspase9. We also observed that DSE significantly decreased the levels of MMP2, MMP9 and VEGF proteins and inhibited the EMT progression in KYSE450 and Eca109 cells. In addition, survivin plays a critical role in DSE against ESCC followed with the application of survivin inhibitor YM155 impairing the inhibitory abilities of DSE in ESCC cells. Meanwhile, it was observed that DSE enhances the sensitivity of DDP to human ESCC cells via promoting DNA damage and inhibiting phosphorylation of STAT3. Therefore, DSE may affect ESCC progression and enhance the sensitivity of cisplatin, and consequently become an effective anti-cancer option for human ESCC treatment.

摘要

与蒲公英一样，蒲公英种子也具有抗炎活性。因此，在本文中，我们旨在探讨蒲公英种子水提取物（DSE）在食管鳞状细胞癌（ESCC）中的抗癌效用。首先，研究了DSE对细胞增殖、凋亡、迁移、侵袭和血管生成的影响。然后，为了探究DSE抗ESCC的机制，分析了增殖相关蛋白（PI3K、Akt和pAkt）、凋亡相关蛋白（survivin、Bcl-2、Bax、caspase3和caspase9）、转移相关蛋白（MMP2、MMP9、VEGF）和EMT进展相关蛋白（Snail、E-钙黏蛋白和波形蛋白）的水平。接下来，我们进一步探讨了DSE对ESCC细胞中顺铂（DDP）敏感性的影响，并研究了DSE联合DDP对DNA损伤修复相关蛋白（MSH2、MLH1和ERCC1）和耐药靶蛋白STAT3的影响。结果表明，DSE选择性抑制ESCC细胞的生长、增殖、迁移、侵袭、血管生成并诱导细胞凋亡。在用DSE处理的KYSE450和Eca109细胞中观察到PI3K、Akt和pAkt蛋白水平降低。数据还显示，应用DSE降低了survivin水平和Bcl-2/Bax比值，同时提高了caspase3和caspase9的水平。我们还观察到，DSE显著降低了KYSE450和Eca109细胞中MMP2、MMP9和VEGF蛋白的水平，并抑制了EMT进展。此外，survivin在DSE抗ESCC中起关键作用，随后应用survivin抑制剂YM155削弱了DSE对ESCC细胞的抑制能力。同时，观察到DSE通过促进DNA损伤和抑制STAT3磷酸化来增强DDP对人ESCC细胞的敏感性。因此，DSE可能影响ESCC进展并增强顺铂的敏感性，从而成为治疗人类ESCC的有效抗癌选择。

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