Purinergic ion channel-type P2X7 receptor regulates SK3 channel to promote the progression of gastric cancer

IF 2.5 4区生物学 Q1 ANATOMY & MORPHOLOGY

Tissue & cell Pub Date : 2025-09-28 DOI:10.1016/j.tice.2025.103162

Pin Wan , Chang-bing Wu

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引用次数: 0

Abstract

The purpose of this study was to investigate the effect of the purinergic ion channel-type P2X7 receptor (P2X7R) on the progression of gastric cancer (GC). Therefore, in this study, in vivo and in vitro experiments were performed to investigate the molecular mechanism of P2X7R on the progression of GC. The results showed that adenosine triphosphate (ATP) and benzoyl ATP (BzATP) activate P2X7R and increased the intracellular calcium concentration of 7901 and 803 cells, and enhanced the migration abilities of GC cells. While P2X7R antagonists (A438079 and AZD9056) decreased the ATP-induced calcium influx, and inhibited the migration abilities of GC cells. This may be related to the stress of actin fibers, which causes the change in cell morphology. Moreover, activation of P2X7R increased the expression of small-conductance Ca^2 + -activated K⁺ channel (SK3) and promoted the migration of GC cells. While A438079 or siRNA transfected cells to knock down the expression of P2X7R and reduced the expression of SK3. The use of SK3 channel inhibitor Apamin inhibited ATP-induced calcium influx and the migration of GC cells. It is interesting that Apamin and A438079 or AZD9056 have a synergistic inhibitory effect. Furthermore, in vivo experiments showed that ATP induced tumor growth, while AZD9056 inhibited ATP-induced tumor growth. Our conclusion is that P2X7R activation promotes the migration and growth of GC cells by opening SK3 channel, and also indicates that P2X7R may become a new potential target for GC treatment.

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嘌呤能离子通道型P2X7受体调控SK3通道促进胃癌的进展。

本研究旨在探讨嘌呤能离子通道型P2X7受体（P2X7R）在胃癌（GC）进展中的作用。因此，本研究通过体内和体外实验探讨P2X7R对GC进展的分子机制。结果表明，三磷酸腺苷（ATP）和苯甲酰ATP （BzATP）能激活P2X7R，增加7901和803细胞内钙浓度，增强GC细胞的迁移能力。而P2X7R拮抗剂（A438079和AZD9056）降低了atp诱导的钙内流，抑制了GC细胞的迁移能力。这可能与肌动蛋白纤维的受力有关，引起细胞形态的改变。此外，P2X7R的激活增加了小电导Ca2 +激活的K+通道（SK3）的表达，促进了GC细胞的迁移。而A438079或siRNA转染细胞，敲低P2X7R的表达，降低SK3的表达。使用SK3通道抑制剂Apamin可抑制atp诱导的钙内流和GC细胞的迁移。有趣的是，Apamin与A438079或AZD9056具有协同抑制作用。此外，体内实验表明，ATP诱导肿瘤生长，而AZD9056抑制ATP诱导的肿瘤生长。我们的结论是P2X7R的激活通过打开SK3通道促进GC细胞的迁移和生长，也表明P2X7R可能成为GC治疗的一个新的潜在靶点。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Tissue & cell 医学-解剖学与形态学

CiteScore

3.90

自引率

0.00%

发文量

234

期刊介绍： Tissue and Cell is devoted to original research on the organization of cells, subcellular and extracellular components at all levels, including the grouping and interrelations of cells in tissues and organs. The journal encourages submission of ultrastructural studies that provide novel insights into structure, function and physiology of cells and tissues, in health and disease. Bioengineering and stem cells studies focused on the description of morphological and/or histological data are also welcomed. Studies investigating the effect of compounds and/or substances on structure of cells and tissues are generally outside the scope of this journal. For consideration, studies should contain a clear rationale on the use of (a) given substance(s), have a compelling morphological and structural focus and present novel incremental findings from previous literature.