IKKα 通过调节 Maspin 在胃癌前病变中的潜在作用。

The potential function of IKKα in gastric precancerous lesion via mediating Maspin.

机构信息

Department of Gastroenterology No.1 Ward, ShiJiaZhuang No. 1 Hospital, Shijiazhuang 050011, China.

出版信息

Tissue Cell. 2020 Aug;65:101349. doi: 10.1016/j.tice.2020.101349. Epub 2020 Mar 2.

DOI:10.1016/j.tice.2020.101349

PMID:32746986

Abstract

OBJECTIVE

To know the potential role of IKKα (an NF-κB noncanonical pathway) in gastric precancerous lesion via mediating Maspin.

METHODS

Gastric cancer, precancerous lesion and control tissues (chronic non-atrophic gastritis) were collected for determining the expression of IKKα and Maspin by immunohistochemistry. Thereafter, gastric precancerous models were established and divided into the Control group, Model group and Model + shIKKα group. All rats were subjected to observe the pathological changes and ultramicro structure of the gastric mucosa by HE staining or electron microscope, and to measure the serum levels of inflammatory cytokines by ELISA, the expression of apoptosis-related proteins by immunohistochemistry, as well as the expression of IKKα and Maspin by quantitative real-time PCR and Western blotting.

RESULTS

Precancerous lesion and gastric cancer tissues manifested significant upregulation of IKKα positive expression, concomitant with downregulation of the positive expression of Maspin, and these changes were more evident in the gastric cancer tissues. In comparison with the Control group, rats in the Model group had significant increases in serum levels of TNF-α, IL-1β, IL-6 and COX-2, with up-regulations of Bcl-2, CyclinD1, IKKα and p-IKKα, and down-regulations of Bax, Caspase-3 and Maspin. shIKKα treatment attenuate inflammation and apoptosis in gastric precancerous lesion (GPL) rat, with the downregulation of IKKα and p-IKKα, and upregulation of Maspin.

CONCLUSION

Inhibiting IKKα, via upregulating Maspin, can mitigate the inflammation and promote cell apoptosis in precancerous rats, thereby delaying the development of the precancerous lesions.

摘要

目的

通过调节 Maspin 来了解 IKKα（NF-κB 非经典途径）在胃癌前病变中的潜在作用。

方法

收集胃癌、癌前病变和对照组织（慢性非萎缩性胃炎），通过免疫组织化学法测定 IKKα 和 Maspin 的表达。然后，建立胃癌前病变模型并分为对照组、模型组和模型+shIKKα 组。所有大鼠均通过 HE 染色或电子显微镜观察胃黏膜的病理变化和超微结构，通过 ELISA 测定血清中炎症细胞因子的水平，通过免疫组织化学法测定凋亡相关蛋白的表达，以及通过实时定量 PCR 和 Western blot 测定 IKKα 和 Maspin 的表达。

结果

癌前病变和胃癌组织中 IKKα 阳性表达明显上调，同时 Maspin 阳性表达下调，且在胃癌组织中变化更为明显。与对照组相比，模型组大鼠血清 TNF-α、IL-1β、IL-6 和 COX-2 水平显著升高，Bcl-2、CyclinD1、IKKα 和 p-IKKα 表达上调，Bax、Caspase-3 和 Maspin 表达下调。shIKKα 治疗可减轻 GPL 大鼠的炎症和细胞凋亡，下调 IKKα 和 p-IKKα，上调 Maspin。