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通过调节HT-29人结肠癌细胞中的基因表达靶向代谢重编程的抗癌作用。

Anti-Cancer Effect of by Targeting Metabolic Reprogramming by Regulating Gene Expression in HT-29 Human Colon Cancer Cells.

作者信息

Ghodousi-Dehnavi Elham, Arjmand Mohammad, Akbari Ziba, Aminzadeh Mansour, Haji Hosseini Reza

机构信息

Department of Biology, Faculty of Science, Payame Noor University, Tehran, Iran.

Metabolomics Lab. Department of Biochemistry, Pasteur Institute of Iran, Pasteur Avenue, Tehran, Iran.

出版信息

Rep Biochem Mol Biol. 2023 Apr;12(1):127-135. doi: 10.52547/rbmb.12.1.127.

Abstract

BACKGROUND

Colorectal cancer is a heterogeneous disease that leads to metabolic disorders due to multiple upstream genetic and molecular changes and interactions. The development of new therapies, especially herbal medicines, has received much global attention. is a medicinal plant. Its gum is used in healing known ailments. Studying metabolome profiles based on nuclear magnetic resonance 1HNMR as a non-invasive and reproducible tool can identify metabolic changes as a reflection of intracellular fluxes, especially in drug responses. This study aimed to investigate the anti-cancer effects of different gum extracts on metabolic changes and their impact on gene expression in HT-29 cell.

METHODS

Extraction of gum with hexane, chloroform, and dichloromethane organic solvents was performed. Cell inhibition growth percentage and IC were assessed. Following treating the cells with dichloromethane extract, , and gene expression were determined. 1HNMR spectroscopy was conducted. Eventually, systems biology software tools interpreted combined metabolites and genes simultaneously.

RESULTS

The lowest determined IC concentration was related to dichloromethane solvent, and the highest was hexane and chloroform. The expression of the oncogene gene decreased significantly after treatment with dichloromethane extract compared to the control group, and the expression of tumor suppressor gene and increased significantly. Most gene-altered convergent metabolic phenotypes.

CONCLUSION

This study's results indicate that the dichloromethane solvent of gum exhibits its antitumor properties by altering the expression of genes involved in HT-29 cells and the consequent change in downstream metabolic reprogramming.

摘要

背景

结直肠癌是一种异质性疾病,由于多种上游基因和分子变化及相互作用导致代谢紊乱。新疗法尤其是草药的开发受到了全球广泛关注。[植物名称]是一种药用植物。其树胶用于治疗已知疾病。基于核磁共振1HNMR作为一种非侵入性且可重复的工具来研究代谢组谱,可以识别作为细胞内通量反映的代谢变化,特别是在药物反应方面。本研究旨在探讨不同树胶提取物对HT - 29细胞代谢变化的抗癌作用及其对基因表达的影响。

方法

用己烷、氯仿和二氯甲烷有机溶剂提取[植物名称]树胶。评估细胞抑制生长百分比和IC。用二氯甲烷提取物处理细胞后,测定[基因名称1]、[基因名称2]和[基因名称3]的基因表达。进行1HNMR光谱分析。最终,系统生物学软件工具同时解释组合的代谢物和基因。

结果

测定的最低IC浓度与二氯甲烷溶剂相关,最高的是己烷和氯仿。与对照组相比,用二氯甲烷提取物处理后癌基因[基因名称1]的表达显著降低,肿瘤抑制基因[基因名称2]和[基因名称3]的表达显著增加。大多数基因改变收敛于代谢表型。

结论

本研究结果表明,[植物名称]树胶的二氯甲烷溶剂通过改变HT - 29细胞中相关基因的表达以及随之而来的下游代谢重编程变化来展现其抗肿瘤特性。

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