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白藜芦醇通过核因子-κB 介导的免疫反应对胃癌的体内抗肿瘤活性。

In vivo antitumour activity of Britanin against gastric cancer through nuclear factor-κB-mediated immune response.

机构信息

Engineering Research Center of Molecular & Neuroimaging, Ministry of Education, School of Life Science and Technology, Xidian University, Xi'an, China.

出版信息

J Pharm Pharmacol. 2020 Apr;72(4):607-618. doi: 10.1111/jphp.13230. Epub 2020 Jan 14.

Abstract

OBJECTIVES

Britanin was explored for the antitumour effect on gastric cancer, which is a sesquiterpene lactone (SL) extracted from Inula japonica.

METHODS

In the present study, cell viability assays were performed to evaluate the antiproliferation effect of Britanin on gastric cancer cells. Tumour development in BGC-823 cell-bearing nude mice was monitored in real-time after Britanin treatment via a bioluminescent imaging method. Western blotting analysis and enzyme-linked immunosorbent assays detected proteins associated with the nuclear factor (NF)-κB signalling pathway.

KEY FINDINGS

Britanin can suppress the proliferation of gastric cancer cells in vitro and the growth of tumours in vivo. In the treatment group, decreased levels of p65 and phosphorylated (p)-p65 were observed. This indicated that NF-κB plays an important role in the antitumour effect of Britanin. Furthermore, considering the additional role of NF-κB in the immune system, the levels of the downstream molecules interleukin (IL)-2 and the cytokine IL-10 were subsequently determined in vivo. An increase in the IL-2 level and a decrease in the IL-10 level indicated that Britanin elicited an enhanced immune response.

CONCLUSIONS

Britanin may be a promising candidate for gastric cancer chemotherapy, and its anticancer effect likely depends on an NF-κB-mediated immune response.

摘要

目的

探讨滨蒿内酯(Britanin)对胃癌的抗肿瘤作用,滨蒿内酯是从菊科植物滨蒿中提取的一种倍半萜内酯(SL)。

方法

本研究采用细胞活力测定法评估 Britanin 对胃癌细胞的增殖抑制作用。通过生物发光成像方法实时监测 BGC-823 荷瘤裸鼠在 Britanin 治疗后的肿瘤发展情况。Western blot 分析和酶联免疫吸附试验检测与核因子(NF)-κB 信号通路相关的蛋白。

主要发现

Britanin 可抑制胃癌细胞在体外的增殖和体内肿瘤的生长。在治疗组中,观察到 p65 和磷酸化(p)-p65 的水平降低。这表明 NF-κB 在 Britanin 的抗肿瘤作用中起重要作用。此外,鉴于 NF-κB 在免疫系统中的额外作用,随后在体内测定下游分子白细胞介素(IL)-2 和细胞因子 IL-10 的水平。IL-2 水平的增加和 IL-10 水平的降低表明 Britanin 引发了增强的免疫反应。

结论

Britanin 可能是一种有前途的胃癌化疗候选药物,其抗癌作用可能依赖于 NF-κB 介导的免疫反应。

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