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塞来昔布治疗对头颈部鳞状细胞癌中AKT信号通路的影响。

Effects of celecoxib treatment over the AKT pathway in head and neck squamous cell carcinoma.

作者信息

Abrahão Aline Corrêa, Giudice Fernanda Salgueiredo, Sperandio Felipe Fornias, Pinto Junior Décio dos Santos

机构信息

Department of Oral Pathology, School of Dentistry, University of São Paulo, São Paulo, Brazil; Department of Pathology and Oral Diagnosis, School of Dentistry, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil.

出版信息

J Oral Pathol Med. 2013 Nov;42(10):793-8. doi: 10.1111/jop.12081. Epub 2013 May 16.

Abstract

BACKGROUND

Celecoxib, a non-steroidal anti-inflammatory drug that selectively inhibits cyclooxygenase-2 (COX-2), has shown an important anticarcinogenic effect for the treatment of squamous cell carcinoma. The use of COX-2 inhibitors has effectively inhibited the growth of Head and Neck Squamous Cell Carcinoma (HNSCC) cell lines, while a recent phase 1 trial demonstrated good response rate of cancer cells to this drug with minimal toxicity. Possible targets of celecoxib include proteins involved in cell proliferation and apoptosis control. Additionally, celecoxib antitumoral activity has been linked with a COX-2-independent event.

METHODS

To better understand which cellular mechanisms are targeted by celecoxib, its effects upon the Akt signaling pathway using two different HNSCC cell lines were analyzed through cell viability assay, immunofluorescence, and Western blotting.

RESULTS

The results showed decreased levels of Cyclin D1 and pAkt protein expression in vitro. The number of viable cells was also diminished after celecoxib treatment.

CONCLUSION

As Akt pathway seems to be a valuable target for the HNSCC therapy, the results presented herein confirm that celecoxib can be considered as an alternative adjuvant drug for HNSCC treatment.

摘要

背景

塞来昔布是一种选择性抑制环氧化酶-2(COX-2)的非甾体抗炎药,已显示出对鳞状细胞癌治疗的重要抗癌作用。COX-2抑制剂的使用有效抑制了头颈部鳞状细胞癌(HNSCC)细胞系的生长,而最近的一项1期试验表明癌细胞对该药物的反应率良好且毒性极小。塞来昔布的可能靶点包括参与细胞增殖和凋亡控制的蛋白质。此外,塞来昔布的抗肿瘤活性与一个不依赖COX-2的事件有关。

方法

为了更好地了解塞来昔布靶向哪些细胞机制,通过细胞活力测定、免疫荧光和蛋白质印迹分析了其对两种不同HNSCC细胞系的Akt信号通路的影响。

结果

结果显示,体外细胞周期蛋白D1和磷酸化Akt蛋白表达水平降低。塞来昔布治疗后活细胞数量也减少。

结论

由于Akt通路似乎是HNSCC治疗的一个有价值的靶点,本文给出的结果证实塞来昔布可被视为HNSCC治疗的一种替代辅助药物。

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