Dong Yun-Fei, Shang Tao
Department of Anorectal, The First Affiliated Hospital of Zhejiang Chinese Medical University (Zhejiang Provincial Hospital of Chinese Medicine), Hangzhou, Zhejiang Province, China.
Turk J Gastroenterol. 2025 Jan 27;36(9):563-572. doi: 10.5152/tjg.2025.24438.
BACKGROUND/AIMS:: Oxidative stress (OS) and inflammation are pivotal for colon cancer (CC) development, which can be regulated by the nuclear factor erythroid 2-related factor 2 (Nrf2) pathway. Matrine (MAT) can treat disorders by modulating OS and inflammation with the Nrf2 pathway. This study aimed to investigate the effects of MAT in CC.
: Mice pretreated with MAT were injected with 1,2-dimethylhydrazine (DMH) to induce CC. Then, colon tissue pathology was examined, and B cell lymphoma-2 (Bcl-2), Bcl-2 associated X (Bax) and antigen identified by monoclonal antibody Ki 67 (Ki-67) expressions in colon tissues were quantified. Moreover, HT-29 cells were treated with MAT and transfected with si-Nrf2 to further investigate the mechanisms of MAT on CC. Following treatment with MAT, the viability and apoptosis of HT-29 cells were detected. Furthermore, OS- and inflammation-related factors, as well as Nrf2 pathway-related expressions, were measured both in vivo and in vitro.
: Matrine treatment alleviated DMH-induced epithelial structural changes, increased Bcl2 and Ki-67 expressions, but decreased Bax expression in the colon. In vitro, MAT inhibited viability but induced apoptosis in HT-29 cells. Both in vivo and in vitro results revealed that MAT alleviated OS and inflammation, increased Nrf2, NAD(P)H quinone dehydrogenase 1, and heme oxygenase-1 expressions, but reduced kelch-like ECH-associated protein 1 expression in CC models. However, the effects of MAT on CC were reversed by Nrf2 knockdown.
: Matrine may alleviate OS and inflammation in CC by activating the Nrf2 pathway, suggesting that MAT may be a promising strategy in CC treatment.
背景/目的：氧化应激（OS）和炎症在结肠癌（CC）的发生发展中起关键作用，其可由核因子红细胞2相关因子2（Nrf2）途径调控。苦参碱（MAT）可通过Nrf2途径调节OS和炎症来治疗疾病。本研究旨在探讨MAT对CC的影响。
用MAT预处理的小鼠注射1,2-二甲基肼（DMH）以诱导CC。然后，检查结肠组织病理学，并对结肠组织中B细胞淋巴瘤-2（Bcl-2）、Bcl-2相关X蛋白（Bax）和单克隆抗体Ki-67识别的抗原（Ki-67）表达进行定量分析。此外，用MAT处理HT-29细胞并转染si-Nrf2以进一步研究MAT对CC的作用机制。用MAT处理后，检测HT-29细胞的活力和凋亡情况。此外，还在体内和体外测量了与OS和炎症相关的因子以及与Nrf2途径相关的表达。
苦参碱治疗减轻了DMH诱导的上皮结构变化，增加了结肠中Bcl2和Ki-67的表达，但降低了Bax的表达。在体外，MAT抑制了HT-29细胞的活力但诱导了其凋亡。体内和体外结果均显示，在CC模型中，MAT减轻了OS和炎症，增加了Nrf2、NAD（P）H醌脱氢酶1和血红素加氧酶-1的表达，但降低了kelch样ECH相关蛋白1的表达。然而，Nrf2基因敲低可逆转MAT对CC的作用。
苦参碱可能通过激活Nrf2途径减轻CC中的OS和炎症，提示MAT可能是CC治疗中有前景的策略。
