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雷弗西定,一种取代嘌呤,通过诱导细胞凋亡和多倍体形成对人肾癌细胞发挥抑制作用。

Reversine, a substituted purine, exerts an inhibitive effect on human renal carcinoma cells via induction of cell apoptosis and polyploidy.

作者信息

Cheng Li, Wang Hao, Guo Kecun, Wang Zicheng, Zhang Zhongyuan, Shen Cheng, Chen Liang, Lin Jian

机构信息

Department of Urology, Peking University First Hospital, Beijing, China.

Institute of Urology, Peking University, Beijing, China.

出版信息

Onco Targets Ther. 2018 Feb 26;11:1025-1035. doi: 10.2147/OTT.S158198. eCollection 2018.

Abstract

BACKGROUND

Human renal cell carcinoma (RCC) is the most common type of kidney cancer that arises from the renal epithelium. Up to 33.3% of RCC patients treated with local tumor resections will subsequently develop recurrence or metastases. Thus, optimized therapeutic regimes are urgently needed to improve the prognosis of RCC. Reversine was recently reported to exert critical roles in cancer therapy.

MATERIALS AND METHODS

This study evaluated the anti-tumor effects of reversine on cell viability, colony formation, apoptosis, and cell cycle in 786-O and ACHN cell lines.

RESULTS

It was demonstrated that reversine significantly inhibited the proliferation of both cell lines in time- and dose-dependent manners. Polyploidy formation was observed under high-concentration reversine treatment. In addition, reversine induced cell death via caspase-dependent apoptotic pathways, which could be partially inhibited by Z-VAD-FMK, a pan-caspase inhibitor.

CONCLUSION

Reversine could effectively suppress the proliferation of human RCC cells, and may serve as a novel therapeutic regimen for RCC in clinical practice.

摘要

背景

人类肾细胞癌(RCC)是起源于肾上皮的最常见的肾癌类型。接受局部肿瘤切除术的RCC患者中,高达33.3%随后会出现复发或转移。因此,迫切需要优化治疗方案以改善RCC的预后。最近有报道称,Reversine在癌症治疗中发挥关键作用。

材料与方法

本研究评估了Reversine对786-O和ACHN细胞系的细胞活力、集落形成、凋亡和细胞周期的抗肿瘤作用。

结果

结果表明,Reversine以时间和剂量依赖性方式显著抑制两种细胞系的增殖。在高浓度Reversine处理下观察到多倍体形成。此外,Reversine通过半胱天冬酶依赖性凋亡途径诱导细胞死亡,一种泛半胱天冬酶抑制剂Z-VAD-FMK可部分抑制这种作用。

结论

Reversine可有效抑制人RCC细胞的增殖,并可能在临床实践中作为RCC的一种新型治疗方案。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4db9/5833753/7b48f87158d8/ott-11-1025Fig1.jpg

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