Single-agent Adavosertib Shows Anticancer Effects Against Colorectal Cancer Cells.

IF 1.6 4区医学 Q4 ONCOLOGY

Anticancer research Pub Date : 2024-11-01 DOI:10.21873/anticanres.17319

Mai Ly Thi Nguyen, Chi Pham, Tai Suc Nguyen, Phuong Linh Thi Nham, Quynh Chi DO, Phuong Linh Tran, Anh Vu Nguyen, Nhu Ngoc Nguyen, Dieu Linh LE, Anh Tho Thi Tran, Thi Lap Nguyen, Przemyslaw Bozko, Linh Toan Nguyen, Khac Cuong Bui

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引用次数: 0

Abstract

Background/aim: Colorectal cancer (CRC) is the third most common malignancy and the second most common cause of cancer-related deaths worldwide. Adavosertib (AZD1775), a small molecule inhibitor of WEE1 kinase, abrogates G₂/M cell cycle arrest and induces double-stranded DNA breaks. According to previous findings, adavosertib, in combination with other DNA-damaging agents, causes premature mitosis and cell death in p53-mutated cancer cells mainly via abrogation of the G₂/M cell cycle checkpoint. This study aims to evaluate the inhibition of WEE1 kinase by adavosertib as monotherapy in the TP53-wildtype human CRC cell line HCT116.

Materials and methods: In this study, HCT116 cells were treated with different concentrations of adavosertib for 24 to 72 hours. Cell viability was assessed by Water-Soluble Tetrazolium 1 (WST-1) assay and crystal violet assays. Cell migration was evaluated by the wound healing assay. Cell cycle distribution and apoptosis were analyzed by flow cytometry.

Results: The IC₅₀ value of adavosertib for the HCT116 cell line was 0.1310 μM. Adavosertib monotherapy (both 0.125 and 0.250 μM) significantly reduced cell viability, inhibited cell migration and abrogated intra-S phase cell cycle arrest. In addition, 0.250 μM of adavosertib significantly induced apoptosis in HCT116 cells.

Conclusion: Adavosertib effectively inhibits the TP53-wildtype HCT116 cells via the abrogation of intra-S phase cell cycle arrest. Our findings suggest that adavosertib monotherapy may be a potential targeted therapy for CRC.

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单药 Adavosertib 对结直肠癌细胞具有抗癌作用

背景/目的：结直肠癌（CRC）是全球第三大常见恶性肿瘤，也是癌症相关死亡的第二大常见原因。阿达沃舍替（AZD1775）是WEE1激酶的一种小分子抑制剂，可抑制G2/M细胞周期停滞并诱导双链DNA断裂。根据之前的研究结果，阿达韦塞替布与其他DNA损伤剂联合使用时，主要通过削弱G2/M细胞周期检查点，导致p53突变癌细胞过早有丝分裂和细胞死亡。本研究旨在评估阿达伐他汀作为单一疗法在TP53野生型人CRC细胞系HCT116中对WEE1激酶的抑制作用：在本研究中，HCT116细胞被不同浓度的阿达伐他汀处理24至72小时。细胞活力通过水溶性四氮唑 1（WST-1）检测法和结晶紫检测法进行评估。通过伤口愈合试验评估细胞迁移。流式细胞术分析了细胞周期分布和细胞凋亡情况：结果：阿达伐塞替布对HCT116细胞株的IC50值为0.1310 μM。Adavosertib 单药治疗（0.125 和 0.250 μM）可显著降低细胞存活率、抑制细胞迁移并终止 S 期细胞周期内的停滞。此外，0.250 μM的阿达韦塞替布能明显诱导HCT116细胞凋亡：结论：阿达吠舍替布通过抑制S期细胞周期内停滞有效抑制了TP53野生型HCT116细胞。我们的研究结果表明，阿达韦塞替布单药疗法可能是治疗 CRC 的一种潜在靶向疗法。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Anticancer research 医学-肿瘤学

CiteScore

3.70

自引率

10.00%

发文量

566

审稿时长

2 months

期刊介绍： ANTICANCER RESEARCH is an independent international peer-reviewed journal devoted to the rapid publication of high quality original articles and reviews on all aspects of experimental and clinical oncology. Prompt evaluation of all submitted articles in confidence and rapid publication within 1-2 months of acceptance are guaranteed. ANTICANCER RESEARCH was established in 1981 and is published monthly (bimonthly until the end of 2008). Each annual volume contains twelve issues and index. Each issue may be divided into three parts (A: Reviews, B: Experimental studies, and C: Clinical and Epidemiological studies). Special issues, presenting the proceedings of meetings or groups of papers on topics of significant progress, will also be included in each volume. There is no limitation to the number of pages per issue.