应用网络药理学预测和实验研究相结合的方法,验证银杏素通过Akt/GSK-3β/Snail和Wnt/β- catenin通路抑制人类肺腺癌细胞侵袭和转移的作用。
Integrating network pharmacology prediction and experimental investigation to verify ginkgetin anti-invasion and metastasis of human lung adenocarcinoma cells via the Akt/GSK-3β/Snail and Wnt/β-catenin pathway.
发表日期:2023
作者:
Kaile Liu, Xiaojie Fu, Zhongqi Wang, Lian Yang, Jia Yang, Haibin Deng
来源:
Cell Death & Disease
摘要:
介绍:肺癌是最常见的恶性肿瘤之一,具有高死亡率和全球新增病例数的增加。银杏被用于肺癌治疗已有多年。银杏素是从银杏中提取的关键活性成分。然而,银杏素抑制肺癌侵袭性转移的机制尚不清楚。方法:我们采用网络药理学方法获取银杏素抑制肺癌转移的分子机制。然后,我们分析了银杏素和肺癌之间的潜在靶蛋白。最后,我们进行了分子对接和实验验证。结果:通过分析肺癌和银杏素的交叉基因,得出了79个交叉基因,主要涉及细胞迁移的正调节,其中癌症通路是最丰富的通路之一。体外实验结果显示,银杏素对A549和H1299细胞的转移和侵袭有很大的抑制作用。在体内动物实验中,银杏素对LLC的转移也有很大的抑制作用。结论:该研究利用网络药理学方法识别了治疗人体肺癌的潜在相关靶标和信号通路。实验证实,银杏素在A549、H1299和LLC细胞中抑制了Akt/GSK-3β/Snail和Wnt/β-catenin级联初始,从而防止了转移。本研究的结果与网络药理学分析得出的假设相符。©2023 Liu、Fu、Wang、Yang、Yang和Deng。
Introduction: 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. Methods: 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. Results: 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 in vitro experiments showed that GK had a large inhibitory effect on cell invasion and metastasis of A549 and H1299. In vivo animals GK had a great inhibitory effect on metastasis of LLC. Conclusion: 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.Copyright © 2023 Liu, Fu, Wang, Yang, Yang and Deng.