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J Gastroenterology: 提高姜黄素的生物利用度并联合NQO1抑制剂对食管鳞状细胞癌有显着的抗肿瘤作用

2019-08-11 不详 MedSci原创

食管鳞状细胞癌(ESCC)是最难治的癌症之一,因此需要开发新的治疗方法来改善患者的预后。姜黄素(Curcumin)是一种来自Curcuma longa的多酚类物质,具有多种健康益处,包括抗肿瘤作用,但由于生物利用度低,其临床应用受到限制。Theracurmin(THC)是分散有胶态亚微米颗粒一个高度生物可利用姜黄素类型。本项研究旨在评估THC在治疗食管鳞状细胞癌中作用。

背景
食管鳞状细胞癌(ESCC)是最难治的癌症之一,因此需要开发新的治疗方法来改善患者的预后。姜黄素(Curcumin)是一种来自Curcuma longa的多酚类物质,具有多种健康益处,包括抗肿瘤作用,但由于生物利用度低,其临床应用受到限制。Theracurmin(THC)是分散有胶态亚微米颗粒一个高度生物可利用姜黄素类型。本项研究旨在评估THC在治疗食管鳞状细胞癌中作用。

方法
研究人员通过细胞活力测定,集落和球状体形成测定以及异种移植模型检查了THC对ESCC细胞的抗肿瘤作用。为了揭示其机制,研究人员研究了活性氧(ROS)的水平并进行了微阵列基因表达分析。根据这些分析,研究人员特别对NQO1进行了研究,NQ01参与了活性氧应激(ROS)的去除,并进行NQO1敲低或过表达对THC治疗的影响。

结果
研究表明THC在ESCC细胞中会引起细胞毒性,并且比姜黄素更有效地抑制异种移植肿瘤的生长。THC增加ROS水平并激活NRF2-NMRAL2P-NQO1表达。通过shRNA或NQO1抑制剂抑制ESCC细胞中的NQO1会导致细胞对THC的敏感性增加,而NQO1的过表达会拮抗这样的现象。值得注意的是,NQO1抑制剂显着增强THC在ESCC PDX肿瘤中的抗肿瘤作用。

结论
本项研究的结果表明THC及其与NQO1抑制剂可以作为治疗ESCC潜在新方法。

原始出处:

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    2020-03-16 jklm09
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    2020-01-18 许安
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    2019-08-13 zhouqu_8
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