Expression of LASS2 Can be Regulated by Dihydroartemisinin to Regulate Cisplatin Chemosensitivity in Bladder Cancer Cells.

IF 2.2 4区医学 Q4 BIOCHEMISTRY & MOLECULAR BIOLOGY

Current pharmaceutical biotechnology Pub Date : 2025-01-01 DOI:10.2174/0113892010305651240514100129

Xuhua Qiao, Rongbo Xue, Shijie Li, Jun Li, Chundong Ji

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Abstract

Introduction: The aim of this study was to investigate the potential of dihydroartemisinin to augment the efficacy of cisplatin chemotherapy through the modulation of LASS2 expression.

Methods: TCMSP, CTR-DB, TCGA-BLC, and other databases were used to analyze the possibility of LASS2 as the target gene of dihydroartemisinin. Cell experiments revealed the synergistic effect of DDP and DHA. Animal experiments showed that DHA inhibited the growth of DDP-treated mice. In addition, WB, real-time PCR, and immunohistochemical analysis showed that DHA enhanced LASS2 (CERS2) expression in bladder cancer cells and DDP-treated mice.

Results: LASS2 is associated with cisplatin chemosensitivity.LASS2 expression levels are different between BLC tissues and normal tissues. COX analysis showed that patients with high LASS2 expression had a higher cumulative overall survival rate than those with low LASS2 expression. The Sankey plot showed that LASS2 expression is lower in BLC tissues with more advanced stage and distant metastasis. The docking score of DHA and LASS2 reached the maximum value of -5.5259, indicating that DHA had a strong binding affinity with LASS2 targets. CCK8 assay showed that the most effective concentration ratio of DHA to DDP was 2.5 μg/ml + 10μg/ml. In vivo experiments showed that DHA inhibited tumor growth in cisplatin-treated mice. In addition, WB, RT-qPCR, and immunohistochemical analysis showed that DHA was able to enhance LASS2 expression in BLC cells and DDP-treated mice.

Conclusion: The upregulation of LASS2 (CERS2) expression in bladder cancer cells by DHA has been found to enhance cisplatin chemosensitivity.

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双氢青蒿素可调控 LASS2 的表达，从而调节膀胱癌细胞对顺铂的化疗敏感性

引言本研究旨在探讨双氢青蒿素通过调节LASS2的表达增强顺铂化疗疗效的潜力：方法：利用TCMSP、CTR-DB、TCGA-BLC等数据库分析LASS2作为双氢青蒿素靶基因的可能性。细胞实验显示了 DDP 和 DHA 的协同作用。动物实验表明，DHA能抑制经DDP处理的小鼠的生长。此外，WB、实时 PCR 和免疫组化分析表明，DHA 可增强膀胱癌细胞和 DDP 处理小鼠中 LASS2（CERS2）的表达：LASS2与顺铂化疗敏感性有关。COX 分析显示，LASS2 高表达患者的累积总生存率高于 LASS2 低表达患者。Sankey图显示，LASS2在晚期和远处转移的BLC组织中表达较低。DHA与LASS2的对接得分达到最大值-5.5259，表明DHA与LASS2靶点有很强的结合亲和力。CCK8实验表明，DHA与DDP的最有效浓度比为2.5μg/ml + 10μg/ml。体内实验表明，DHA 可抑制顺铂治疗小鼠的肿瘤生长。此外，WB、RT-qPCR和免疫组化分析表明，DHA能够提高BLC细胞和DDP处理小鼠体内LASS2的表达：结论：DHA能上调膀胱癌细胞中LASS2（CERS2）的表达，从而增强顺铂的化学敏感性。

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

Current pharmaceutical biotechnology 医学-生化与分子生物学

CiteScore

5.60

自引率

3.60%

发文量

203

审稿时长

6 months

期刊介绍： Current Pharmaceutical Biotechnology aims to cover all the latest and outstanding developments in Pharmaceutical Biotechnology. Each issue of the journal includes timely in-depth reviews, original research articles and letters written by leaders in the field, covering a range of current topics in scientific areas of Pharmaceutical Biotechnology. Invited and unsolicited review articles are welcome. The journal encourages contributions describing research at the interface of drug discovery and pharmacological applications, involving in vitro investigations and pre-clinical or clinical studies. Scientific areas within the scope of the journal include pharmaceutical chemistry, biochemistry and genetics, molecular and cellular biology, and polymer and materials sciences as they relate to pharmaceutical science and biotechnology. In addition, the journal also considers comprehensive studies and research advances pertaining food chemistry with pharmaceutical implication. Areas of interest include: DNA/protein engineering and processing Synthetic biotechnology Omics (genomics, proteomics, metabolomics and systems biology) Therapeutic biotechnology (gene therapy, peptide inhibitors, enzymes) Drug delivery and targeting Nanobiotechnology Molecular pharmaceutics and molecular pharmacology Analytical biotechnology (biosensing, advanced technology for detection of bioanalytes) Pharmacokinetics and pharmacodynamics Applied Microbiology Bioinformatics (computational biopharmaceutics and modeling) Environmental biotechnology Regenerative medicine (stem cells, tissue engineering and biomaterials) Translational immunology (cell therapies, antibody engineering, xenotransplantation) Industrial bioprocesses for drug production and development Biosafety Biotech ethics Special Issues devoted to crucial topics, providing the latest comprehensive information on cutting-edge areas of research and technological advances, are welcome. Current Pharmaceutical Biotechnology is an essential journal for academic, clinical, government and pharmaceutical scientists who wish to be kept informed and up-to-date with the latest and most important developments.