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气味糖苷A对肺癌的凋亡、促氧化及治疗作用评估:一项体外研究并对人肺癌数据集进行计算机模拟分析的扩展研究

Evaluation of the Apoptotic, Prooxidative and Therapeutic Effects of Odoroside A on Lung Cancer: An In Vitro Study Extended with In Silico Analyses of Human Lung Cancer Datasets.

作者信息

Çelik Fatma Seçer, Şengül Göksemin Fatma, Altveş Safaa, Eroğlu Güneş Canan

机构信息

Department of Medical Biology and Genetics, Faculty of Medicine, Ankara Medipol University, 06050 Ankara, Turkey.

Department of Medical Biochemistry, Faculty of Medicine, Ankara Medipol University, 06050 Ankara, Turkey.

出版信息

Life (Basel). 2025 Mar 12;15(3):445. doi: 10.3390/life15030445.

Abstract

OBJECTIVE

The apoptotic effects of odoroside A on lung cancer cells were studied in our project. We also supported and extended our experimentally-proven results via bioinformatics analysis on human lung cancer tissues.

MATERIALS AND METHODS

In vitro studies were conducted using the A549 cell line. Cell proliferation was evaluated through a CCK-8 assay. For gene expression analysis, the qRT-PCR method was used, while CASP3 protein levels were detected using Western blotting and ELISA. Moreover, the oxidant status of cells was determined by measuring TAS and TOS levels. To construct a protein-protein interaction network, STRING analysis was performed. For the determination of differential expression of apoptosis-related genes, the GEPIA tool was utilized. Kaplan-Meier plots with overall survival, disease-specific survival and progression free intervals were obtained from UCSC Xena to evaluate the prognostic value of caspases.

RESULTS

The gene expression levels of , , , , , and were elevated between 4-16 fold in Odo A-treated lung cancer cells compared to controls. CASP3 protein expression was significantly higher in Odo A-treated cancerous cells than the control group. Low TAS (0.5700 ± 0.0067 in Odo A vs. 0.6437 ± 0.0151 in control) and high TOS (0.82800 ± 0.0208 in Odo A vs. 0.6263 ± 0.0258 in control) levels as well as high OSI values (1.4531 ± 0.0414 in Odo A vs. 0.9748 ± 0.0539 in control) were obtained. Correlogram and protein-protein network analyses suggested strong correlations and interactions among target genes. Lastly, Kaplan-Meier analysis showed no prognostic value of caspases, but potential therapeutic targets in lung cancer.

CONCLUSIONS

Anti-cancer, prooxidative and therapeutic effects of Odo A on lung cancer cells were shown in our study. These data were supported and extended via computational analyses that we performed. In conclusion, Odo A could be used in clinics to treat patients with lung cancer.

摘要

目的

本项目研究了奥多索苷A对肺癌细胞的凋亡作用。我们还通过对人肺癌组织的生物信息学分析来支持和扩展我们的实验验证结果。

材料与方法

使用A549细胞系进行体外研究。通过CCK-8试验评估细胞增殖。基因表达分析采用qRT-PCR方法,而使用蛋白质印迹法和酶联免疫吸附测定法检测半胱天冬酶3(CASP3)蛋白水平。此外,通过测量总抗氧化能力(TAS)和总氧化应激(TOS)水平来确定细胞的氧化状态。为构建蛋白质-蛋白质相互作用网络,进行了STRING分析。为确定凋亡相关基因的差异表达,使用了GEPIA工具。从加州大学圣克鲁兹分校的Xena数据库获得了总生存期、疾病特异性生存期和无进展生存期的Kaplan-Meier图,以评估半胱天冬酶的预后价值。

结果

与对照组相比,奥多索苷A处理的肺癌细胞中,[此处原文缺失相关基因名称]、[此处原文缺失相关基因名称]、[此处原文缺失相关基因名称]、[此处原文缺失相关基因名称]、[此处原文缺失相关基因名称]和[此处原文缺失相关基因名称]的基因表达水平升高了4至16倍。奥多索苷A处理的癌细胞中CASP3蛋白表达明显高于对照组。奥多索苷A组的总抗氧化能力水平较低(奥多索苷A组为0.5700±0.0067,对照组为0.6437±0.0151),总氧化应激水平较高(奥多索苷A组为0.82800±0.0208,对照组为0.6263±0.0258),氧化应激指数(OSI)值也较高(奥多索苷A组为1.4531±0.0414,对照组为0.9748±0.0539)。相关图和蛋白质-蛋白质网络分析表明靶基因之间存在强相关性和相互作用。最后,Kaplan-Meier分析显示半胱天冬酶无预后价值,但在肺癌中具有潜在的治疗靶点。

结论

我们的研究表明奥多索苷A对肺癌细胞具有抗癌、促氧化和治疗作用。我们通过进行的计算分析支持并扩展了这些数据。总之,奥多索苷A可用于临床治疗肺癌患者。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/778f/11944172/1e5f4989fa74/life-15-00445-g001.jpg

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