Chao Sun , Qiushuang Ma , Liya Feng, Jianbo Ji, Dandan Du, Pengfei Shang, Xiuli Guo
{"title":"mcp增强的SOD3活性通过调节EGFR信号抑制胃癌并增强化疗。","authors":"Chao Sun , Qiushuang Ma , Liya Feng, Jianbo Ji, Dandan Du, Pengfei Shang, Xiuli Guo","doi":"10.1016/j.lfs.2024.123358","DOIUrl":null,"url":null,"abstract":"<div><h3>Aims</h3><div>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).</div></div><div><h3>Materials and methods</h3><div>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.</div></div><div><h3>Key findings</h3><div>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.</div></div><div><h3>Significance</h3><div>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.</div></div>","PeriodicalId":18122,"journal":{"name":"Life sciences","volume":"362 ","pages":"Article 123358"},"PeriodicalIF":5.2000,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"MCP-enhanced SOD3 activity inhibits gastric cancer and potentiate chemotherapy via modulating EGFR signaling\",\"authors\":\"Chao Sun , Qiushuang Ma , Liya Feng, Jianbo Ji, Dandan Du, Pengfei Shang, Xiuli Guo\",\"doi\":\"10.1016/j.lfs.2024.123358\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><h3>Aims</h3><div>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).</div></div><div><h3>Materials and methods</h3><div>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.</div></div><div><h3>Key findings</h3><div>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.</div></div><div><h3>Significance</h3><div>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.</div></div>\",\"PeriodicalId\":18122,\"journal\":{\"name\":\"Life sciences\",\"volume\":\"362 \",\"pages\":\"Article 123358\"},\"PeriodicalIF\":5.2000,\"publicationDate\":\"2025-02-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Life sciences\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://www.sciencedirect.com/science/article/pii/S0024320524009482\",\"RegionNum\":2,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"MEDICINE, RESEARCH & EXPERIMENTAL\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Life sciences","FirstCategoryId":"3","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S0024320524009482","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"MEDICINE, RESEARCH & EXPERIMENTAL","Score":null,"Total":0}
MCP-enhanced SOD3 activity inhibits gastric cancer and potentiate chemotherapy via modulating EGFR signaling
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.
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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