文章：

Gαi2蛋白抑制阻断化疗及抗雄激素诱导的前列腺癌细胞迁移

Gαi2 Protein Inhibition Blocks Chemotherapy- and Anti-Androgen-Induced Prostate Cancer Cell Migration

原文发布日期：10 January 2024

DOI: 10.3390/cancers16020296

类型: Article

开放获取: 是

英文摘要：

We have previously shown that heterotrimeric G-protein subunit alphai2 (Gαi2) is essential for cell migration and invasion in prostate, ovarian and breast cancer cells, and novel small molecule inhibitors targeting Gαi2 block its effects on migratory and invasive behavior. In this study, we have identified potent, metabolically stable, second generation Gαi2 inhibitors which inhibit cell migration in prostate cancer cells. Recent studies have shown that chemotherapy can induce the cancer cells to migrate to distant sites to form metastases. In the present study, we determined the effects of taxanes (docetaxel), anti-androgens (enzalutamide and bicalutamide) and histone deacetylase (HDAC) inhibitors (SAHA and SBI-I-19) on cell migration in prostate cancer cells. All treatments induced cell migration, and simultaneous treatments with new Gαi2 inhibitors blocked their effects on cell migration. We concluded that a combination treatment of Gαi2 inhibitors and chemotherapy could blunt the capability of cancer cells to migrate and form metastases.

摘要翻译： 

我们先前的研究表明，异源三聚体G蛋白亚基αi2（Gαi2）在前列腺癌、卵巢癌和乳腺癌细胞的迁移与侵袭过程中起着关键作用，而针对Gαi2的新型小分子抑制剂能够阻断其对细胞迁移和侵袭行为的调控。本研究成功鉴定出具有高效代谢稳定性的第二代Gαi2抑制剂，可显著抑制前列腺癌细胞的迁移能力。近期研究表明，化疗可能诱导癌细胞向远处迁移并形成转移灶。在本研究中，我们系统评估了紫杉烷类药物（多西他赛）、抗雄激素药物（恩杂鲁胺与比卡鲁胺）以及组蛋白去乙酰化酶抑制剂（SAHA和SBI-I-19）对前列腺癌细胞迁移的影响。所有治疗均能诱导细胞迁移，而新型Gαi2抑制剂的联合应用可完全阻断这种促迁移效应。我们得出结论：Gαi2抑制剂与化疗药物的联合治疗方案能够有效抑制癌细胞的迁移及转移灶形成能力。

原文链接：

Gαi2 Protein Inhibition Blocks Chemotherapy- and Anti-Androgen-Induced Prostate Cancer Cell Migration