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整合网络药理学预测与实验研究以验证白果素对人肺腺癌细胞侵袭和转移的抑制作用及对Akt/GSK-3β/Snail和Wnt/β-连环蛋白信号通路的影响

Integrating network pharmacology prediction and experimental investigation to verify ginkgetin anti-invasion and metastasis of human lung adenocarcinoma cells the Akt/GSK-3β/Snail and Wnt/β-catenin pathway.

作者信息

Liu Kaile, Fu Xiaojie, Wang Zhongqi, Yang Lian, Yang Jia, Deng Haibin

机构信息

Department of Oncology, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, China.

出版信息

Front Pharmacol. 2023 Mar 2;14:1135601. doi: 10.3389/fphar.2023.1135601. eCollection 2023.

Abstract

Lung cancer, one of the most frequent malignancies, has a high death rate and an increased number of new cases globally. Ginkgo biloba has been used for many years in the treatment of lung cancer. Ginkgetin is the key active ingredient extracted from Ginkgo biloba. However, the mechanism by which ginkgetin inhibits the invasive metastasis of lung cancer is unclear. We used a network pharmacology approach to obtain the molecular mechanism by which ginkgetin inhibits lung cancer metastasis. Then we analyzed potential target proteins between ginkgetin and lung cancer. Finally, we validated with molecular docking and experimental validation. By analyzing the intersecting genes of lung cancer and ginkgetin, there were 79 intersecting genes, which were mainly involved in the positive regulation of cell migration, with the cancer pathway being one of the most enriched pathways. The results of experiments showed that GK had a large inhibitory effect on cell invasion and metastasis of A549 and H1299. animals GK had a great inhibitory effect on metastasis of LLC. This study identified the potential related GK molecular targets and signaling pathways in treating human lung cancer using network pharmacological approaches. Experiments confirmed that GK inhibits the Akt/GSK-3β/Snail and Wnt/β-catenin cascade initiation in A549, H1299 and LLC cells, preventing metastasis. This study's results align with the hypotheses derived from the network pharmacology analysis.

摘要

肺癌是最常见的恶性肿瘤之一,全球死亡率高且新发病例数不断增加。银杏已被用于治疗肺癌多年。银杏黄素是从银杏中提取的关键活性成分。然而,银杏黄素抑制肺癌侵袭转移的机制尚不清楚。我们采用网络药理学方法来获得银杏黄素抑制肺癌转移的分子机制。然后我们分析了银杏黄素与肺癌之间的潜在靶蛋白。最后,我们通过分子对接和实验验证进行了验证。通过分析肺癌与银杏黄素的交集基因,共有79个交集基因,主要参与细胞迁移的正调控,癌症通路是最富集的通路之一。实验结果表明,银杏黄素对A549和H1299细胞的侵袭和转移有较大抑制作用。在动物实验中,银杏黄素对LLC的转移有很大抑制作用。本研究利用网络药理学方法确定了银杏黄素在治疗人类肺癌中的潜在相关分子靶点和信号通路。实验证实,银杏黄素抑制A549、H1299和LLC细胞中的Akt/GSK-3β/Snail和Wnt/β-连环蛋白级联启动,从而防止转移。本研究结果与网络药理学分析得出的假设一致。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/19f3/10018034/06d73eaada2c/fphar-14-1135601-g001.jpg

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