Chitosan nanoparticles, camel milk exosomes and/or Sorafenib induce apoptosis, inhibit tumor cells migration and angiogenesis and ameliorate the associated liver damage in Ehrlich ascites carcinoma-bearing mice

IF 2.5 Q2 MULTIDISCIPLINARY SCIENCES

Beni-Suef University Journal of Basic and Applied Sciences Pub Date : 2024-08-02 DOI:10.1186/s43088-024-00535-4

Amr A. Tawfic, Hany M. Ibrahim, Khaled Mohammed-Geba, Mohammed A. El-Magd

{"title":"Chitosan nanoparticles, camel milk exosomes and/or Sorafenib induce apoptosis, inhibit tumor cells migration and angiogenesis and ameliorate the associated liver damage in Ehrlich ascites carcinoma-bearing mice","authors":"Amr A. Tawfic, Hany M. Ibrahim, Khaled Mohammed-Geba, Mohammed A. El-Magd","doi":"10.1186/s43088-024-00535-4","DOIUrl":null,"url":null,"abstract":"<div><h3>Background</h3><p>It is crucial to improve cancer patients' quality of life by developing medications that can treat cancer with minimum adverse effects. This study aimed to evaluate the therapeutic effect of chitosan nanoparticles (CNPs) and camel milk exosomes (CMEs) alone or in combination with Sorafenib (SOR) on Ehrlich ascites carcinoma (EAC)-bearing mice and to assess whether EAC-associated liver injury would be ameliorated due to this combination. Liver function and oxidant/antioxidant status were determined spectrophotometrically, while the levels of inflammatory cytokines were estimated by enzyme-linked immunosorbent assay. Gene expression was detected using real-time polymerase chain reaction.</p><h3>Results</h3><p>The tumor burden in EAC-bearing mice was reduced after treatment with CNPs ± CMEs ± SOR as indicated by (1) reduced ascetic fluid volume and tumor-cell viability; (2) induction of apoptosis [high p53, BCL2 associated X<i> (Bax</i>)<i>,</i> caspase 3, low B-cell leukemia/lymphoma 2 protein (<i>Bcl2</i>)]; (3) increased intracellular reactive oxygen species; (4) decreased migration [high matrix metalloproteinase 9 (<i>MMP9</i>) and low TIMP metallopeptidase inhibitor 1 (<i>TIMP1</i>)]; (5) declined angiogenesis [low vascular endothelial growth factor (<i>VEGF</i>). These treatments also reduced liver injury induced by EAC as noticed by (1) restored liver function indices [alanine transaminase (ALT), aspartate transaminase (AST), alkaline phosphatase (ALP), and albumin]; (2) restored redox balance [low malondialdehyde (MDA) levels and high superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx) activities]; (3) increased antioxidant gene expression [high nuclear factor erythroid 2-related factor 2 (<i>Nrf2</i>) and heme oxygenase-1 (<i>HO-1</i>)]; (4) declined inflammation [low interleukin-1β (IL1β) and tumor necrosis factor alpha<b> (</b>TNFα) levels), and (5) enhanced structure of liver. SOR + CNPs-treated mice showed the most improvement, followed by SOR + CMEs-treated animals.</p><h3>Conclusions</h3><p>Based on these findings, we determined that CNPs and CMEs enhanced SOR's anticancer efficacy and had an ameliorative role against EAC-induced liver injuries.</p><h3>Graphic abstract</h3><div><figure><div><div><picture><source><img></source></picture></div></div></figure></div></div>","PeriodicalId":481,"journal":{"name":"Beni-Suef University Journal of Basic and Applied Sciences","volume":"13 1","pages":""},"PeriodicalIF":2.5000,"publicationDate":"2024-08-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://bjbas.springeropen.com/counter/pdf/10.1186/s43088-024-00535-4","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Beni-Suef University Journal of Basic and Applied Sciences","FirstCategoryId":"1085","ListUrlMain":"https://link.springer.com/article/10.1186/s43088-024-00535-4","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"MULTIDISCIPLINARY SCIENCES","Score":null,"Total":0}

引用次数: 0

Abstract

Background

It is crucial to improve cancer patients' quality of life by developing medications that can treat cancer with minimum adverse effects. This study aimed to evaluate the therapeutic effect of chitosan nanoparticles (CNPs) and camel milk exosomes (CMEs) alone or in combination with Sorafenib (SOR) on Ehrlich ascites carcinoma (EAC)-bearing mice and to assess whether EAC-associated liver injury would be ameliorated due to this combination. Liver function and oxidant/antioxidant status were determined spectrophotometrically, while the levels of inflammatory cytokines were estimated by enzyme-linked immunosorbent assay. Gene expression was detected using real-time polymerase chain reaction.

Results

The tumor burden in EAC-bearing mice was reduced after treatment with CNPs ± CMEs ± SOR as indicated by (1) reduced ascetic fluid volume and tumor-cell viability; (2) induction of apoptosis [high p53, BCL2 associated X (Bax), caspase 3, low B-cell leukemia/lymphoma 2 protein (Bcl2)]; (3) increased intracellular reactive oxygen species; (4) decreased migration [high matrix metalloproteinase 9 (MMP9) and low TIMP metallopeptidase inhibitor 1 (TIMP1)]; (5) declined angiogenesis [low vascular endothelial growth factor (VEGF). These treatments also reduced liver injury induced by EAC as noticed by (1) restored liver function indices [alanine transaminase (ALT), aspartate transaminase (AST), alkaline phosphatase (ALP), and albumin]; (2) restored redox balance [low malondialdehyde (MDA) levels and high superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx) activities]; (3) increased antioxidant gene expression [high nuclear factor erythroid 2-related factor 2 (Nrf2) and heme oxygenase-1 (HO-1)]; (4) declined inflammation [low interleukin-1β (IL1β) and tumor necrosis factor alpha (TNFα) levels), and (5) enhanced structure of liver. SOR + CNPs-treated mice showed the most improvement, followed by SOR + CMEs-treated animals.

Conclusions

Based on these findings, we determined that CNPs and CMEs enhanced SOR's anticancer efficacy and had an ameliorative role against EAC-induced liver injuries.

Graphic abstract

查看原文本刊更多论文

壳聚糖纳米颗粒、骆驼奶外泌体和/或索拉非尼诱导艾氏腹水癌小鼠凋亡、抑制肿瘤细胞迁移和血管生成，并改善相关肝损伤

通过开发可治疗癌症且不良反应最小的药物来提高癌症患者的生活质量至关重要。本研究旨在评估壳聚糖纳米颗粒（CNPs）和骆驼奶外泌体（CMEs）单独或与索拉非尼（SOR）联合使用对艾氏腹水癌（EAC）小鼠的治疗效果，并评估联合使用是否会减轻EAC相关的肝损伤。肝功能和氧化剂/抗氧化剂状态用分光光度法测定，炎症细胞因子水平用酶联免疫吸附法估测。基因表达采用实时聚合酶链反应检测。使用 CNPs ± CMEs ± SOR 治疗后，EAC 小鼠的肿瘤负荷减轻，表现在：（1）腹水体积和肿瘤细胞存活率降低；（2）诱导细胞凋亡[p53、BCL2 相关 X（Bax）、caspase 3 高，B 细胞白血病/淋巴瘤 2 蛋白（Bcl2）低]；(3) 细胞内活性氧增加；(4) 迁移减少[基质金属蛋白酶 9 (MMP9) 高，TIMP 金属肽酶抑制剂 1 (TIMP1) 低]；(5) 血管生成减少[血管内皮生长因子 (VEGF) 低]。这些治疗也减轻了 EAC 引起的肝损伤，具体表现在：(1) 肝功能指标[丙氨酸转氨酶（ALT）、天门冬氨酸转氨酶（AST）、碱性磷酸酶（ALP）和白蛋白]得到恢复；(2) 氧化还原平衡得到恢复[丙二醛（MDA）水平低，超氧化物歧化酶（SOD）、过氧化氢酶（CAT）和谷胱甘肽过氧化物酶（GPx）活性高]；(3) 抗氧化基因表达增加[核因子红细胞 2 相关因子 2（Nrf2）和血红素加氧酶-1（HO-1）含量高]；(4) 炎症减少[白细胞介素-1β（IL1β）和肿瘤坏死因子α（TNFα）含量低]；以及 (5) 肝脏结构增强。经 SOR + CNPs 处理的小鼠病情改善最大，其次是经 SOR + CMEs 处理的动物。基于这些发现，我们确定 CNPs 和 CMEs 可增强 SOR 的抗癌功效，并对 EAC 诱导的肝损伤有改善作用。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

求助全文

约1分钟内获得全文求助全文

来源期刊

Beni-Suef University Journal of Basic and Applied Sciences MULTIDISCIPLINARY SCIENCES-

CiteScore

2.60

自引率

0.00%

发文量

期刊介绍： Beni-Suef University Journal of Basic and Applied Sciences (BJBAS) is a peer-reviewed, open-access journal. This journal welcomes submissions of original research, literature reviews, and editorials in its respected fields of fundamental science, applied science (with a particular focus on the fields of applied nanotechnology and biotechnology), medical sciences, pharmaceutical sciences, and engineering. The multidisciplinary aspects of the journal encourage global collaboration between researchers in multiple fields and provide cross-disciplinary dissemination of findings.