研究动态
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多儿玛天然树胶通过调节HT-29人结肠癌细胞中的代谢重编程,通过调控APC、P53和KRAS基因表达,实现了抗癌效应。

Anti-Cancer Effect of Dorema Ammoniacum Gum by Targeting Metabolic Reprogramming by Regulating APC, P53, KRAS Gene Expression in HT-29 Human Colon Cancer Cells.

发表日期:2023 Apr
作者: Elham Ghodousi-Dehnavi, Mohammad Arjmand, Ziba Akbari, Mansour Aminzadeh, Reza Haji Hosseini
来源: Genes & Diseases

摘要:

结直肠癌是一种异质性疾病,由于多种上游的遗传和分子变化和相互作用导致代谢紊乱。新疗法的发展,特别是草药疗法,已经引起了全球的关注。阿胶是一种药用植物,其胶可用于治疗已知疾病。基于核磁共振1HNMR的代谢组分析作为一种非侵入性和可重复性工具,可以鉴定代谢变化,作为细胞内通量的反映,特别是在药物反应中。本研究旨在研究不同胶提取物对代谢变化的抗癌作用以及对HT-29细胞基因表达的影响。使用正己烷、氯仿和二氯甲烷有机溶剂对阿胶胶进行提取。评估细胞抑制生长百分比和IC50。将细胞处理二氯甲烷提取物后,确定了p53、APC和KRAS基因的表达。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。确定的最低IC50浓度与二氯甲烷溶剂有关,而最高浓度则是正己烷和氯仿。与对照组相比,经过二氯甲烷提取物处理后,KRAS癌基因的表达显著下降,而抑癌基因p53和APC的表达显著上升。多种基因改变交汇的代谢表型。本研究的结果表明,阿胶胶的二氯甲烷溶剂通过改变参与HT-29细胞的基因表达以及随之而来的下游代谢重编程而表现出其抗肿瘤特性。
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. Dorema ammoniacum 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.Extraction of Dorema ammoniacum gum with hexane, chloroform, and dichloromethane organic solvents was performed. Cell inhibition growth percentage and IC50 were assessed. Following treating the cells with dichloromethane extract, p53, APC, and KRAS gene expression were determined. 1HNMR spectroscopy was conducted. Eventually, systems biology software tools interpreted combined metabolites and genes simultaneously.The lowest determined IC50 concentration was related to dichloromethane solvent, and the highest was hexane and chloroform. The expression of the KRAS oncogene gene decreased significantly after treatment with dichloromethane extract compared to the control group, and the expression of tumor suppressor gene p53 and APC increased significantly. Most gene-altered convergent metabolic phenotypes.This study's results indicate that the dichloromethane solvent of Dorema ammoniacum gum exhibits its antitumor properties by altering the expression of genes involved in HT-29 cells and the consequent change in downstream metabolic reprogramming.