Downregulation of LncRNA CCAT1 Enhances Chemosensitivity in Cisplatin-Resistant Gastric Cancer Cells

IF 3.5 4区医学 Q2 CHEMISTRY, MEDICINAL

Drug Development Research Pub Date : 2025-01-20 DOI:10.1002/ddr.70048

Qiong Wu, Chenglou Zhu, Tiantian Zhao, Tianxiang Liu, Mingxu Da

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引用次数: 0

Abstract

Chemotherapy is an effective treatment for gastric cancer. However, many patients develop resistance to chemotherapeutic agents during clinical treatment. LncRNA CCAT1 has recently been shown to influence cellular resistance to specific chemotherapeutic drugs, but its role in gastric cancer remains underexplored. This study aims to investigate the role of LncRNA CCAT1 in cisplatin resistance in gastric cancer cells and its potential underlying mechanisms. Gastric cancer cell lines with acquired resistance were established. The expression of CCAT1 was assessed in both cisplatin-sensitive and cisplatin-resistant AGS cell lines. CCAT1 expression was knocked down in AGS/DDP cells, and the changes in IC50 values were measured using the Cell Counting Kit-8 (CCK-8) assay. Apoptosis in gastric cancer cells was evaluated by flow cytometry. Additionally, Western blotting was employed to measure the expression levels of PI3K/AKT/mTOR signaling pathway proteins and apoptosis-related proteins in both interference and control groups. RT-qPCR results indicated that CCAT1 expression was significantly elevated in cisplatin-resistant gastric cancer cells compared to non-resistant cells. Similarly, CCK-8 assay results demonstrated that knocking down CCAT1 in resistant cells increased their sensitivity to cisplatin treatment. Flow cytometry and Western blot results further confirmed that silencing CCAT1 promoted apoptosis in these cells. Additionally, the expression of PI3K/AKT/mTOR signaling pathway proteins was higher in resistant cells compared to their sensitive counterparts, and silencing CCAT1 in AGS/DDP cells resulted in reduced expression of these proteins. In conclusion, the above studies demonstrated that LncRNA CCAT1 induced cisplatin resistance in gastric cancer cells.

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LncRNA CCAT1的下调增强顺铂耐药胃癌细胞的化疗敏感性

化疗是治疗胃癌的有效方法。然而，在临床治疗过程中，许多患者对化疗药物产生耐药性。LncRNA CCAT1最近被证明影响细胞对特定化疗药物的耐药性，但其在胃癌中的作用仍未被充分探索。本研究旨在探讨LncRNA CCAT1在胃癌细胞顺铂耐药中的作用及其潜在机制。建立了获得性耐药胃癌细胞系。CCAT1在顺铂敏感和顺铂耐药AGS细胞系中的表达均被评估。在AGS/DDP细胞中下调CCAT1的表达，使用细胞计数试剂盒-8 （CCK-8）测定IC50值的变化。采用流式细胞术观察胃癌细胞凋亡的变化。Western blotting检测干扰组和对照组细胞中PI3K/AKT/mTOR信号通路蛋白和凋亡相关蛋白的表达水平。RT-qPCR结果显示，与非耐药细胞相比，CCAT1在顺铂耐药胃癌细胞中的表达明显升高。同样，CCK-8检测结果表明，敲除耐药细胞中的CCAT1可增加其对顺铂治疗的敏感性。流式细胞术和Western blot结果进一步证实，沉默CCAT1可促进这些细胞的凋亡。此外，PI3K/AKT/mTOR信号通路蛋白在耐药细胞中的表达高于敏感细胞，而在AGS/DDP细胞中沉默CCAT1导致这些蛋白的表达降低。综上所述，上述研究表明LncRNA CCAT1诱导胃癌细胞产生顺铂耐药。

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来源期刊

Drug Development Research 医学-药学

CiteScore

6.40

自引率

2.60%

发文量

104

审稿时长

6-12 weeks

期刊介绍： Drug Development Research focuses on research topics related to the discovery and development of new therapeutic entities. The journal publishes original research articles on medicinal chemistry, pharmacology, biotechnology and biopharmaceuticals, toxicology, and drug delivery, formulation, and pharmacokinetics. The journal welcomes manuscripts on new compounds and technologies in all areas focused on human therapeutics, as well as global management, health care policy, and regulatory issues involving the drug discovery and development process. In addition to full-length articles, Drug Development Research publishes Brief Reports on important and timely new research findings, as well as in-depth review articles. The journal also features periodic special thematic issues devoted to specific compound classes, new technologies, and broad aspects of drug discovery and development.