The effects of Abemaciclib on cell cycle and apoptosis regulation in anaplastic thyroid cancer cells,Molecular Biology Reports

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The effects of Abemaciclib on cell cycle and apoptosis regulation in anaplastic thyroid cancer cells
Molecular Biology Reports ( IF 2.6 ) Pub Date : 2023-03-06 , DOI: 10.1007/s11033-023-08255-1
Elaheh S Abutorabi _{1,

2} , Arash Poursheikhani ₃ , Bahareh Kashani ₁ , Sahar Shamsaiegahkani ₁ , Vahid Haghpanah ₄ , Davood Bashash ₅ , Seied A Mousavi ₁ , Majid Momeny ₆ , Seyed H Ghaffari ₁

Affiliation

Background:

Anaplastic thyroid cancer (ATC) is an aggressive subtype of thyroid cancer, accounting for 1 to 2% of all cases. Deregulations of cell cycle regulatory genes including cyclins, cyclin-dependent kinases (CDKs), and endogenous inhibitors of CDKs (CKIs) are hallmarks of cancer cells and hence, studies indicate the inhibition of CDK4/6 kinases and cell cycle progression as potent therapeutic strategies. In this study, we investigated the anti-tumor activity of Abemaciclib, a CDK4 and CDK6 inhibitor, in ATC cell lines.

Methods and results:

The ATC cell lines C643 and SW1736 were selected to study the antiproliferative effects of Abemaciclib using a cell proliferation assay and crystal violet staining assay. Annexin V/PI staining and cell cycle analysis by flow cytometry were also performed to examine the effects on apoptosis induction and cell cycle arrest. Wound healing assay and zymography analysis examined the effects of the drug on invasive abilities of ATC cells and Western blot analyses were applied to further study the anti-tumor mechanism of Abemaciclib, in addition to combination treatment with alpelisib. Our data demonstrated that Abemaciclib significantly inhibited cell proliferation and increased cellular apoptosis and cell cycle arrest in ATC cell lines, while considerably reducing cell migration and colony formation. The mechanism seemed to involve the PI3K pathway.

Conclusion:

Our preclinical data highlight CDK4/6 as interesting therapeutic targets in ATC and suggest CDK4/6-blockade therapies as promising strategies in this malignancy.

中文翻译：

Abemaciclib对未分化甲状腺癌细胞周期和凋亡调控的影响

背景：

间变性甲状腺癌 (ATC) 是甲状腺癌的一种侵袭性亚型，占所有病例的 1% 至 2%。细胞周期调节基因（包括细胞周期蛋白、细胞周期蛋白依赖性激酶 (CDK) 和内源性 CDK 抑制剂 (CKI)）的失调是癌细胞的标志，因此，研究表明抑制 CDK4/6 激酶和细胞周期进程是有效的治疗策略. 在这项研究中，我们研究了 Abemaciclib（一种 CDK4 和 CDK6 抑制剂）在 ATC 细胞系中的抗肿瘤活性。

方法与结果：

选择 ATC 细胞系 C643 和 SW1736 以使用细胞增殖试验和结晶紫染色试验研究 Abemaciclib 的抗增殖作用。还进行了膜联蛋白 V/PI 染色和流式细胞术细胞周期分析，以检查对细胞凋亡诱导和细胞周期停滞的影响。伤口愈合试验和酶谱分析检查了药物对 ATC 细胞侵袭能力的影响，并应用蛋白质印迹分析进一步研究 Abemaciclib 的抗肿瘤机制，以及与 alpelisib 的联合治疗。我们的数据表明，Abemaciclib 显着抑制 ATC 细胞系中的细胞增殖并增加细胞凋亡和细胞周期停滞，同时显着减少细胞迁移和集落形成。该机制似乎涉及 PI3K 通路。