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罗哌卡因通过SNX10/SRC/STAT3途径抑制胃癌细胞的增殖和转移。

Ropivacaine inhibits the proliferation and metastasis of gastric cancer cells via the SNX10/SRC/STAT3 pathway.

作者信息

Deng Rong-Rong, Yuan You-Ping

机构信息

Department of Anaesthesiology, Wujin Hospital Affiliated with Jiangsu University, Changzhou, China.

Department of Anaesthesiology, The Wujin Clinical College of Xuzhou Medical University, Changzhou, China.

出版信息

Chem Biol Drug Des. 2024 Jan;103(1):e14405. doi: 10.1111/cbdd.14405. Epub 2023 Nov 21.

DOI:10.1111/cbdd.14405
PMID:37989501
Abstract

Gastric cancer currently has no effective treatment due to its high metastasis and heterogeneity. It has been reported that ropivacaine (Rop) can inhibit the growth, migration, and invasion of gastric cancer. However, the therapeutic mechanism of Rop still needs to be further explored to provide insights for its clinical application. This study aimed to explore the effects of Rop on the growth, migration, and invasion of gastric cancer cells and the underlying mechanisms. The expression levels of SNX10 were assessed in gastric cancer tissues and cell line AGS by qRT-PCR. Cell Counting Kit-8 (CCK8) assay, wound-healing assay, and transwell assay were then used to examine the effects of Rop on the AGS cell viability, migration, invasion, and proliferation, respectively. Additionally, colony formation assay was used to measure cell proliferation ability, and flow cytometry was used to detect apoptosis level. Protein levels of SNX10, SRC, and STAT3 were detected by western blot. According to the experimental results, the decreased SNX10 mRNA expression was observed in gastric cancer tissue and cell line AGS. Rop inhibited the proliferation, migration, and invasion of AGS cells, but promoted apoptosis and upregulated SNX10 expression. Moreover, Rop inhibited the expression of MMP-2 and MMP-9, phosphorylation of SRC and STAT3. SNX10 knockdown could reverse Rop-induced anticancer effects. Collectively, Rop showed a potential role in preventing proliferation and metastasis of gastric cancer. The action mechanism of Rop may be related to the upregulation of SNX10 expression and further inhibition of SRC/STAT3 signaling pathway. Our findings provide new insights into the anticancer properties of Rop.

摘要

由于胃癌具有高转移性和异质性,目前尚无有效的治疗方法。据报道,罗哌卡因(Rop)可抑制胃癌的生长、迁移和侵袭。然而,Rop的治疗机制仍需进一步探索,以便为其临床应用提供依据。本研究旨在探讨Rop对胃癌细胞生长、迁移和侵袭的影响及其潜在机制。通过qRT-PCR评估胃癌组织和细胞系AGS中SNX10的表达水平。然后分别使用细胞计数试剂盒-8(CCK8)检测、伤口愈合检测和Transwell检测来研究Rop对AGS细胞活力、迁移、侵袭和增殖的影响。此外,采用集落形成检测来测量细胞增殖能力,流式细胞术用于检测细胞凋亡水平。通过蛋白质印迹法检测SNX10、SRC和STAT3的蛋白水平。根据实验结果,在胃癌组织和细胞系AGS中观察到SNX10 mRNA表达降低。Rop抑制AGS细胞的增殖、迁移和侵袭,但促进细胞凋亡并上调SNX10表达。此外,Rop抑制MMP-2和MMP-9的表达、SRC和STAT3的磷酸化。敲低SNX10可逆转Rop诱导的抗癌作用。总体而言,Rop在预防胃癌增殖和转移方面显示出潜在作用。Rop的作用机制可能与上调SNX10表达以及进一步抑制SRC/STAT3信号通路有关。我们的研究结果为Rop的抗癌特性提供了新的见解。

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