RNPEP调控巨噬细胞焦亡参与胃癌细胞的生物学行为的分子机制

doi:10.3969/j.issn.1006-6233.2024.11.011

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摘要 目的:探究RNPEP调控巨噬细胞焦亡对胃癌细胞的生物学行为的影响及可能机制。方法:收集临床正常胃组织与胃癌组织各10例,RT-qPCR检测正常组织与胃癌组织中RNPEP的mRNA水平。培养THP-1细胞并诱导为M0巨噬细胞,分为对照组与过表达RNPEP组。Western blotting检侧巨噬细胞中RNPEP、细胞焦亡相关蛋白GSDME、NLRP3、IL-1β、IL-18蛋白表达水平。将人胃腺癌细胞MGC-803与对照组、过表达RNPEP组M0巨噬细胞共培养,分为对照组与过表达RNPEP组。共培养MGC-803细胞与过表达RNPEP组的M0巨噬细胞,向两组培养液中分别加入IL-1β IgG1同型抗体与IL-1β IgG1中和抗体,分为过表达RNPEP组与抑制IL-1β组。EdU试剂盒检测MGC-803胃癌细胞的增殖能力。Transwell实验检测MGC-803胃癌细胞的侵袭能力。划痕实验检测MGC-803胃癌细胞的迁移能力。结果:与正常组织相比,胃癌组织中RNPEP的mRNA水平增加(P<0.05)。与对照组相比,过表达RNPEP组巨噬细胞中RNPEP、细胞焦亡相关蛋白GSDME、NLRP3、IL-1β、IL-18蛋白表达增加(P<0.05)。与对照组相比,过表达RNPEP组胃癌细胞MGC-803增殖、迁移、侵袭能力增加(P<0.05)。与过表达RNPEP组相比,抑制IL-1β组胃癌细胞MGC-803增殖、迁移、侵袭能力减少(P<0.05)。结论:分泌蛋白RNPEP可上调巨噬细胞焦亡促进胃癌细胞的生物学行为。

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关键词 ：胃癌, RNPEP, 巨噬细胞焦亡, 增殖, 侵袭, 迁移

Abstract：Objective: To investigate the effect of RNPEP on the biological behavior of gastric cancer cells and its possible mechanism.Methods: RNPEP mRNA levels in normal gastric tissues and gastric cancer tissues were detected by RT-qPCR. THP-1 cells were cultured and induced into M0 macrophages, which were divided into control group and RNPEP overexpression group. The expression levels of RNPEP, GSDME, NLRP3, IL-1β and IL-18 in macrophages were detected by Western blotting. Human gastric adenocarcinoma cell MGC-803 was co-cultured with M0 macrophages of the control and RNPEP overexpression groups, and divided into control group and RNPEP overexpression group. MGC-803 cells and M0 macrophages in the over-expressing RNPEP group were co-cultured, and IL-1β IgG1 homologous antibody and IL-1β IgG1 neutralizing antibody were added to the culture medium of the two groups, respectively, and they were divided into the RNPEP over-expression group and the inhibiting IL-1β group. The proliferation ability of MGC-803 gastric cancer cells was detected by EdU kit. The invasive ability of MGC-803 gastric cancer cells was detected by Transwell assay. The migration ability of MGC-803 gastric cancer cells was detected by scratch test.Results: Compared with normal tissues, mRNA level of RNPEP was increased in gastric cancer tissues (P<0.05). Compared with the control group, the expressions of RNPEP, GSDME, NLRP3, IL-1β, and IL-18 in macrophages of the RNPEP over-expression group were increased (P<0.05). Compared with the control group, the proliferation, migration and invasion ability of MGC-803 cells in the RNPEP over-expression group were increased (P<0.05). Compared with the RNPEP over-expression group, the proliferation, migration, and invasion ability of MGC-803 cells in IL-1β inhibition group were decreased (P<0.05).Conclusion:The secreted protein RNPEP can promote the biological behavior of gastric cancer cells by up-regulating pyroptosis of macrophages.

Key words： Gastric cancer RNPEP Macrophage pyroptosis Proliferation Invade Migration

基金资助:河北省卫生健康委员会科研项目,(编号:20220047)

通讯作者: 薛佳栋

引用本文:

霍亚楠, 杨晨, 郭书丽, 路宽, 李慎, 郭天, 薛佳栋. RNPEP调控巨噬细胞焦亡参与胃癌细胞的生物学行为的分子机制[J]. 河北医学, 2024, 30(11): 1820-1824.
HUO Ya'nan, YANG Chen, GUO Shuli, et al. Molecular Mechanisms of RNPEP-Regulated Macrophage Pyrodeath Involved in the Biological Behaviour of Gastric Cancer Cells. HeBei Med, 2024, 30(11): 1820-1824.

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http://www.hbyxzzs.cn/CN/10.3969/j.issn.1006-6233.2024.11.011 或 http://www.hbyxzzs.cn/CN/Y2024/V30/I11/1820

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