Hong Ye, Li Yanrong, Liu Xia, Deng Jia, He Yanli, Zhao Bin
Center of Digestive Endoscopy, Shaanxi Provincial Cancer Hospital No. 309 Yanta West Road, Yanta District, Xi'an 710061, Shaanxi, China.
Department of Gastroenterology, Baoji People's Hospital No. 24 Xinhua Lane, Jing'er Road, Weibin District, Baoji 721000, Shaanxi, China.
Am J Cancer Res. 2025 Mar 15;15(3):929-945. doi: 10.62347/KELA7583. eCollection 2025.
Colorectal cancer (CRC) is a prevalent and highly lethal malignancy, with current therapeutic efficacy limited by the tumor's high invasiveness and metastatic potential. Matrix metalloproteinases (MMPs) and the WNT (Wingless/Integrated) signaling pathway play key roles in the invasion and metastasis of CRC. Salidroside, a natural compound, has demonstrated inhibitory effects in several cancers, but its precise molecular mechanism in CRC cells remains unclear. This study aims to investigate the antitumor effect of salidroside on CRC and its molecular mechanism in influencing epithelial-mesenchymal transition (EMT) by regulating MMP-12 and the WNT signaling pathway. The effects of salidroside on CRC cell proliferation, migration, and invasion were evaluated through in vitro experiments using HCT-116 and SW620 cell lines. The antitumor effects of salidroside were validated using CCK-8, wound healing, and Transwell assays. Expression changes of MMP-12, WNT signaling-related proteins (e.g., β-catenin, GSK-3β), and EMT markers (e.g., E-cadherin, Vimentin) after salidroside treatment were measured by qRT-PCR and Western Blot. Additionally, bioinformatics analysis was performed using TCGA and GEO databases in combination with the BEST online tool to identify differentially expressed genes, followed by GSEA enrichment analysis. Salidroside showed significant antiproliferative and inhibitory effects on the migration and invasion of CRC cells. In vitro experiments demonstrated that salidroside significantly inhibited CRC cell proliferation and reduced their migration and invasion capabilities. qRT-PCR and Western Blot analyses showed that salidroside significantly downregulated MMP-12 expression and led to changes in the expression of WNT signaling and EMT-related proteins, specifically downregulating β-catenin, upregulating E-cadherin, and downregulating Vimentin. Furthermore, bioinformatics analysis indicated that MMP-12 plays a crucial role in salidroside-mediated CRC inhibition, further supporting its potential as a key target. In conclusion, salidroside suppresses CRC invasion and migration by downregulating MMP-12 and modulating the WNT signaling pathway, thereby inhibiting the EMT process. These findings suggest that salidroside holds potential as a therapeutic agent for CRC, offering a novel approach to CRC treatment.
结直肠癌（CRC）是一种常见且具有高度致死性的恶性肿瘤，目前的治疗效果受到肿瘤高侵袭性和转移潜能的限制。基质金属蛋白酶（MMPs）和WNT（无翅/整合）信号通路在CRC的侵袭和转移中起关键作用。红景天苷是一种天然化合物，已在多种癌症中显示出抑制作用，但其在CRC细胞中的精确分子机制仍不清楚。本研究旨在探讨红景天苷对CRC的抗肿瘤作用及其通过调节MMP-12和WNT信号通路影响上皮-间质转化（EMT）的分子机制。通过使用HCT-116和SW620细胞系进行体外实验，评估红景天苷对CRC细胞增殖、迁移和侵袭的影响。使用CCK-8、伤口愈合和Transwell实验验证红景天苷的抗肿瘤作用。通过qRT-PCR和蛋白质免疫印迹法检测红景天苷处理后MMP-12、WNT信号相关蛋白（如β-连环蛋白、糖原合成酶激酶-3β）和EMT标志物（如E-钙黏蛋白、波形蛋白）的表达变化。此外，结合TCGA和GEO数据库并使用BEST在线工具进行生物信息学分析，以鉴定差异表达基因，随后进行基因集富集分析（GSEA）。红景天苷对CRC细胞的增殖以及迁移和侵袭具有显著的抑制作用。体外实验表明，红景天苷显著抑制CRC细胞增殖，并降低其迁移和侵袭能力。qRT-PCR和蛋白质免疫印迹分析表明，红景天苷显著下调MMP-12表达，并导致WNT信号和EMT相关蛋白表达的变化，具体表现为下调β-连环蛋白、上调E-钙黏蛋白和下调波形蛋白。此外，生物信息学分析表明，MMP-12在红景天苷介导的CRC抑制中起关键作用，进一步支持其作为关键靶点的潜力。总之，红景天苷通过下调MMP-12和调节WNT信号通路抑制CRC的侵袭和迁移，从而抑制EMT过程。这些发现表明，红景天苷具有作为CRC治疗药物的潜力，为CRC治疗提供了一种新方法。
