Ma Xuran, Wang Dunfang, Liu Yaqing, Liu Bin, Feng Xue, Yang Weipeng
Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing, China.
Institute of Pharmaceutical Research, Shandong University of Traditional Chinese Medicine. Jinan, China.
Heliyon. 2023 Feb 25;9(3):e13739. doi: 10.1016/j.heliyon.2023.e13739. eCollection 2023 Mar.
Chronic inflammation is usually caused by persistent irritation or uncontrolled infection and is characterized by ongoing tissue damage, injury-induced cellular proliferation and tissue repair. Colitis-associated colorectal cancer (CAC) isone of the classic examples of tumors that are tightly related to chronic inflammation.
To investigated the key pharmacodynamic genes of HQT interventions in CAC by using transcriptome predictions and experiments.Materials & Methods: We used the azoxymethane/dextran sodium sulfate method to induce the mice CAC model. After preventive administration of HQT to the mice model, colonic tissues were taken for transcriptome sequencing and the transcriptome results were then experimentally validated using quantitative Real-Time PCR technique.
Transcriptome sequencing revealed that the effect of the mechanism of HQT on the CAC mice model maybe related to its inhibition of accelerated epithelial mesenchymal transition and induction of pyroptosis. The levels of Matrix-metalloproteinases such as MMP-2, MMP-9 were significantly reduced in CAC mice treated with HQT; The mRNA expression for Krt17, App, CD44 and WNT pathway related sites such as Lrrc15, Cldn-1, Mpc1, Agr2 which are related factors affecting the epithelial mesenchymal transition were significantly reduced in CAC mice treated with HQT; the aberrant mRNA expression of inflammasome components that drive pyroptosis, including Nlrp3, Caspase-1, ASC, GSDMD and its mediated product IL-18 have been improved.
Our findings provide preliminary clarification that inhibiting the progression of CAC by using HQT is effective, the mechanism of action may be relatedto the inhibition of epithelial mesenchymal transition and induction of pyroptosis during tumorigenesis.
慢性炎症通常由持续刺激或不受控制的感染引起，其特征是持续的组织损伤、损伤诱导的细胞增殖和组织修复。结肠炎相关结直肠癌（CAC）是与慢性炎症密切相关的肿瘤的经典例子之一。
通过转录组预测和实验研究槐角丸（HQT）干预CAC的关键药效基因。
采用氧化偶氮甲烷/葡聚糖硫酸钠法诱导小鼠CAC模型。对小鼠模型预防性给予HQT后，取结肠组织进行转录组测序，然后使用定量实时PCR技术对转录组结果进行实验验证。
转录组测序显示，HQT作用于CAC小鼠模型的机制可能与其抑制上皮间质转化加速和诱导细胞焦亡有关。用HQT处理的CAC小鼠中，基质金属蛋白酶如MMP-2、MMP-9的水平显著降低；用HQT处理的CAC小鼠中，影响上皮间质转化的相关因子如Krt17、App、CD44以及WNT通路相关位点如Lrrc15、Cldn-1、Mpc1、Agr2的mRNA表达显著降低；驱动细胞焦亡的炎性小体成分的异常mRNA表达，包括Nlrp3、Caspase-1、ASC、GSDMD及其介导产物IL-18均得到改善。
我们的研究结果初步阐明，使用HQT抑制CAC进展是有效的，其作用机制可能与肿瘤发生过程中抑制上皮间质转化和诱导细胞焦亡有关。
