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伐地考昔可恢复结肠癌细胞系中的脂质组成、有序性及动力学,且与COX-2表达无关:一项衰减全反射傅里叶变换红外光谱研究

Valdecoxib Recovers the Lipid Composition, Order and Dynamics in Colon Cancer Cell Lines Independent of COX-2 Expression: An ATR-FTIR Spectroscopy Study.

作者信息

Inan Genç Aysun, Gok Seher, Banerjee Sreeparna, Severcan Feride

机构信息

Department of Biological Sciences, Middle East Technical University, Turkey.

出版信息

Appl Spectrosc. 2017 Jan;71(1):105-117. doi: 10.1177/0003702816654164. Epub 2016 Jul 20.

Abstract

Prostanoids play an important role in a variety of physiological and pathophysiological processes including inflammation and cancer. The rate-limiting step in the prostanoid biosynthesis pathway is catalyzed by cyclooxygenases (COXs). Aberrant expression of the inducible isoform COX-2 plays a significant role in colon cancer initiation and progression. In this study, we have hypothesized that COX-2 specific inhibitors such as Valdecoxib (VLX), being highly hydrophobic, may alter biophysical properties of cellular lipids. In this study, COX-2 expressing (HT29) and COX-2 non-expressing (SW620) colon cancer cell lines were treated with VLX and examined using attenuated total reflection infrared spectroscopy. The results revealed that VLX treatment decreased lipid fluidity in the cells irrespective of COX-2 expression status and affected order parameters of the lipids in both cell lines. Cluster analysis also indicated that the spectral differences between the two cell lines are profound and could be successfully differentiated. Valdecoxib treatment could enhance the composition, order and dynamics of the lipids of colon cancer cells independently of its COX-2 inhibitory mechanism. Valdecoxib has therapeutic effects upon colon cancer, therefore it can be used as an adjuvant and/or chemopreventive agent for colon cancer.

摘要

前列腺素在包括炎症和癌症在内的多种生理和病理生理过程中发挥着重要作用。前列腺素生物合成途径中的限速步骤由环氧化酶(COXs)催化。诱导型异构体COX-2的异常表达在结肠癌的发生和发展中起重要作用。在本研究中,我们假设COX-2特异性抑制剂如伐地考昔(VLX),因其高度疏水,可能会改变细胞脂质的生物物理性质。在本研究中,用VLX处理表达COX-2的(HT29)和不表达COX-2的(SW620)结肠癌细胞系,并使用衰减全反射红外光谱进行检测。结果显示,无论COX-2表达状态如何,VLX处理均会降低细胞中的脂质流动性,并影响两种细胞系中脂质的有序参数。聚类分析还表明,两种细胞系之间的光谱差异很大,并且可以成功区分。伐地考昔治疗可独立于其COX-2抑制机制增强结肠癌细胞脂质的组成、有序性和动力学。伐地考昔对结肠癌具有治疗作用,因此可作为结肠癌的辅助和/或化学预防剂。

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