Proteomic Analysis of the Molecular Mechanisms of Chlorpromazine Inhibiting Migration of Oral Squamous Cell Carcinoma

IF 0.5 4区生物学 Q4 BIOCHEMICAL RESEARCH METHODS Current Proteomics Pub Date : 2024-02-27 DOI:10.2174/0115701646291510240212091951

Nannan Zhang, Junzhi Liu, Qiuping Dong, Chen Liu, Xinyu Liang, Peiyuan Tang, Zheng Liang

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Abstract

Background: Oral squamous cell carcinoma (OSCC) is a common malignant tumor of the head and neck region known for its high metastatic and invasive potential. Chlorpromazine (CPZ) has been shown to inhibit the growth of oral cancer cells. However, the effects of CPZ on OSCC migration and its underlying molecular mechanisms remain unclear. Objective: We aimed to identify global protein changes and potential core proteins involved in CPZ-mediated inhibition of migration in SCC-15 cells using proteomics. Methods: We assessed the effect of CPZ on SCC-15 using CCK-8 assays and wound healing experiments. Next, we performed LC-MS-based proteomic analysis to identify protein alterations in SCC-15 cells treated with CPZ at different times. Differential expression proteins (DEPs) were identified and subjected to bioinformatics analysis using GO, KEGG, and PPI tools. Key candidate proteins were selected and validated using the TCGA-HNSCC database and molecular docking. Results: It was found that 20μm of CPZ had no effect on cell proliferation, but inhibited cell migration. A total of 4748 proteins were identified by Proteomics, among which 56 DEPs were identified, including 34 upregulated proteins and 22 downregulated proteins. Three proteins (RPF2, ACTB, and TGFBI) were identified as key candidate proteins associated with cell adhesion and migration in oral cancer cells. Conclusion: CPZ may affect the expression of RPF2, ACTB, and TGFBI proteins and change the extracellular matrix and cell adhesion function, thus inhibiting the migration of SCC-15 cells. The results of this study provide a robust basis for further research on the molecular mechanism of CPZ to inhibit the migration of OSCC.

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氯丙嗪抑制口腔鳞状细胞癌迁移的分子机制蛋白质组学分析

背景：口腔鳞状细胞癌（OSCC）是头颈部常见的恶性肿瘤，具有高转移性和侵袭性。氯丙嗪（CPZ）已被证明能抑制口腔癌细胞的生长。然而，CPZ 对 OSCC 迁移的影响及其潜在的分子机制仍不清楚。研究目的我们的目的是利用蛋白质组学鉴定 CPZ 介导的 SCC-15 细胞迁移抑制所涉及的全局蛋白变化和潜在核心蛋白。方法：我们评估了 CPZ 对 SCC-15 细胞迁移的影响：我们使用 CCK-8 试验和伤口愈合实验评估了 CPZ 对 SCC-15 的影响。接着，我们进行了基于 LC-MS 的蛋白质组学分析，以确定不同时间用 CPZ 处理的 SCC-15 细胞中的蛋白质变化。我们利用 GO、KEGG 和 PPI 工具鉴定了差异表达蛋白（DEPs）并对其进行了生物信息学分析。利用 TCGA-HNSCC 数据库和分子对接技术筛选并验证了关键候选蛋白。结果发现结果发现，20μm 的 CPZ 对细胞增殖没有影响，但抑制了细胞迁移。蛋白质组学共鉴定出4748个蛋白质，其中56个DEPs，包括34个上调蛋白质和22个下调蛋白质。三个蛋白质（RPF2、ACTB和TGFBI）被确定为与口腔癌细胞粘附和迁移相关的关键候选蛋白质。结论CPZ 可能会影响 RPF2、ACTB 和 TGFBI 蛋白的表达，改变细胞外基质和细胞粘附功能，从而抑制 SCC-15 细胞的迁移。本研究结果为进一步研究 CPZ 抑制 OSCC 迁移的分子机制提供了有力依据。

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来源期刊

Current Proteomics BIOCHEMICAL RESEARCH METHODS-BIOCHEMISTRY & MOLECULAR BIOLOGY

CiteScore

1.60

自引率

0.00%

发文量

审稿时长

>0 weeks

期刊介绍： Research in the emerging field of proteomics is growing at an extremely rapid rate. The principal aim of Current Proteomics is to publish well-timed in-depth/mini review articles in this fast-expanding area on topics relevant and significant to the development of proteomics. Current Proteomics is an essential journal for everyone involved in proteomics and related fields in both academia and industry. Current Proteomics publishes in-depth/mini review articles in all aspects of the fast-expanding field of proteomics. All areas of proteomics are covered together with the methodology, software, databases, technological advances and applications of proteomics, including functional proteomics. Diverse technologies covered include but are not limited to: Protein separation and characterization techniques 2-D gel electrophoresis and image analysis Techniques for protein expression profiling including mass spectrometry-based methods and algorithms for correlative database searching Determination of co-translational and post- translational modification of proteins Protein/peptide microarrays Biomolecular interaction analysis Analysis of protein complexes Yeast two-hybrid projects Protein-protein interaction (protein interactome) pathways and cell signaling networks Systems biology Proteome informatics (bioinformatics) Knowledge integration and management tools High-throughput protein structural studies (using mass spectrometry, nuclear magnetic resonance and X-ray crystallography) High-throughput computational methods for protein 3-D structure as well as function determination Robotics, nanotechnology, and microfluidics.