二甲双胍通过抑制FAK/Akt信号通路抑制宫颈癌迁移。
Metformin Inhibit Cervical Cancer Migration by Suppressing the FAK/Akt Signaling Pathway.
作者信息
Hakimee Henna, Hutamekalin Pilaiwanwadee, Tanasawet Supita, Chonpathompikunlert Pennapa, Tipmanee Varomyalin, Sukketsiri Wanida
机构信息
Department of Pharmacology, Faculty of Science, Prince of Songkla University, Hat Yai, Songkhla, Thailand.
Department of Physiology, Faculty of Science, Prince of Songkla University, Hat Yai, Songkhla,Thailand.
出版信息
Asian Pac J Cancer Prev. 2019 Dec 1;20(12):3539-3545. doi: 10.31557/APJCP.2019.20.12.3539.
BACKGROUND
Metformin, an antidiabetic drug, has been previously reported to have anti-cancer activities. However, its role in the control of cancer cell migration remains elusive.
METHODS
To examine the possible effect of metformin on migration of cervical cancer cells. The related mechanisms were further determined by immunocytochemistry and Western's blotting assay.
RESULTS
The results showed that metformin treatment substantially inhibited the migration ability of cervical cancer cells. Consistently, the filopodia and lamellipodia formation were depleted after exposure to metformin. The suppression of migration mediated through the regulatory proteins such as focal adhesion kinase (FAK), ATP-dependent tyrosine kinase (Akt), Rac1 and RhoA after metformin treatment.
CONCLUSION
Metformin displays antimigration effects in cervical cancer cells by inhibiting filopodia and lamellipodia formation through the suppression of FAK, Akt and its downstream Rac1 and RhoA protein. We propose that metformin could be a novel potential candidate as an antimetastatic cancer drug in the cervical cancer management.
背景
二甲双胍是一种抗糖尿病药物，此前有报道称其具有抗癌活性。然而，其在控制癌细胞迁移方面的作用仍不清楚。
方法
为了研究二甲双胍对宫颈癌细胞迁移的可能影响。通过免疫细胞化学和蛋白质印迹分析进一步确定相关机制。
结果
结果表明，二甲双胍处理显著抑制了宫颈癌细胞的迁移能力。同样，暴露于二甲双胍后，丝状伪足和片状伪足的形成减少。二甲双胍处理后，通过诸如粘着斑激酶（FAK）、ATP依赖性酪氨酸激酶（Akt）、Rac1和RhoA等调节蛋白介导的迁移受到抑制。
结论
二甲双胍通过抑制丝状伪足和片状伪足的形成，抑制FAK、Akt及其下游的Rac1和RhoA蛋白，从而在宫颈癌细胞中发挥抗迁移作用。我们认为，二甲双胍可能是宫颈癌治疗中一种新型的潜在抗转移癌药物。
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