MCP-enhanced SOD3 activity inhibits gastric cancer and potentiate chemotherapy via modulating EGFR signaling

IF 5.2 2区 医学 Q1 MEDICINE, RESEARCH & EXPERIMENTAL Life sciences Pub Date : 2025-02-01 DOI:10.1016/j.lfs.2024.123358
Chao Sun , Qiushuang Ma , Liya Feng, Jianbo Ji, Dandan Du, Pengfei Shang, Xiuli Guo
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Abstract

Aims

This study aims to investigate the role of SOD3 in gastric cancer (GC) progression and its impact on chemotherapy efficacy and toxicity. It further seeks to evaluate the therapeutic potential of MCP in enhancing SOD3 activity to improve treatment outcomes and reduce chemotherapy-induced peripheral neurotoxicity (CIPN).

Materials and methods

We used overexpression plasmids and small interfering RNAs (siRNAs) to modulate the expression of SOD3 and Desmocollin2 (DSC2) in gastric cancer cells. Molecular biology experiments were performed to analyze pathway-related protein expression and molecular interactions. In vitro and in vivo experiments were conducted to evaluate the effects of modified citrus pectin (MCP) and oxaliplatin (OXA), individually and in combination, on gastric cancer progression and CIPN.

Key findings

SOD3 inhibited the proliferation, migration, and invasion of GC cells via SOD3/EGFR/PKP3/DSC2 axis. MCP selectively increased SOD3 levels and enhanced its anti-tumor effects. Combined treatment with MCP and OXA synergistically inhibited GC progression in vitro and in vivo, while MCP alleviated CIPN, enabling OXA dose reduction without compromising efficacy.

Significance

The findings revealed that SOD3 played a critical tumor-suppressive role in gastric cancer by modulating the SOD3/EGFR/PKP3/DSC2 axis. MCP, a natural compound that selectively boosted SOD3 levels, enhanced chemotherapy efficacy while reducing peripheral neurotoxicity, providing a promising strategy to improve gastric cancer treatment and mitigate chemotherapy-related side effects.

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mcp增强的SOD3活性通过调节EGFR信号抑制胃癌并增强化疗。
目的:本研究旨在探讨SOD3在胃癌(GC)进展中的作用及其对化疗疗效和毒性的影响。该研究进一步寻求评估MCP在提高SOD3活性以改善治疗结果和减少化疗诱导的周围神经毒性(CIPN)方面的治疗潜力。材料和方法:我们利用过表达质粒和小干扰rna (sirna)调节胃癌细胞中SOD3和Desmocollin2 (DSC2)的表达。通过分子生物学实验分析通路相关蛋白表达及分子间相互作用。通过体外和体内实验,评价改性柑橘果胶(MCP)和奥沙利铂(OXA)单独或联合使用对胃癌进展和CIPN的影响。主要发现:SOD3通过SOD3/EGFR/PKP3/DSC2轴抑制GC细胞的增殖、迁移和侵袭。MCP选择性提高SOD3水平,增强抗肿瘤作用。MCP和OXA联合治疗在体外和体内协同抑制GC进展,而MCP减轻CIPN,使OXA剂量减少而不影响疗效。意义:研究结果表明SOD3通过调节SOD3/EGFR/PKP3/DSC2轴在胃癌中发挥重要的抑瘤作用。MCP是一种天然化合物,可选择性地提高SOD3水平,增强化疗疗效,同时降低周围神经毒性,为改善胃癌治疗和减轻化疗相关副作用提供了一种有希望的策略。
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来源期刊
Life sciences
Life sciences 医学-药学
CiteScore
12.20
自引率
1.60%
发文量
841
审稿时长
6 months
期刊介绍: Life Sciences is an international journal publishing articles that emphasize the molecular, cellular, and functional basis of therapy. The journal emphasizes the understanding of mechanism that is relevant to all aspects of human disease and translation to patients. All articles are rigorously reviewed. The Journal favors publication of full-length papers where modern scientific technologies are used to explain molecular, cellular and physiological mechanisms. Articles that merely report observations are rarely accepted. Recommendations from the Declaration of Helsinki or NIH guidelines for care and use of laboratory animals must be adhered to. Articles should be written at a level accessible to readers who are non-specialists in the topic of the article themselves, but who are interested in the research. The Journal welcomes reviews on topics of wide interest to investigators in the life sciences. We particularly encourage submission of brief, focused reviews containing high-quality artwork and require the use of mechanistic summary diagrams.
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