Xie Yiwen, Xu Sumei, Chen Zhiyun, Song Caiping, Yan Wenxi
Department of General Practice, The First Affiliated Hospital of Zhejiang Chinese Medical University (Zhejiang Provincial Hospital of Chinese Medicine), Hangzhou, Zhejiang, China.
Key Laboratory of Integrative Chinese and Western Medicine for the Diagnosis and Treatment of Circulatory Diseases of Zhejiang Province, The First Affiliated Hospital of Zhejiang Chinese Medical University (Zhejiang Provincial Hospital of Chinese Medicine), Hangzhou, Zhejiang, China.
Front Oncol. 2024 Aug 2;14:1414766. doi: 10.3389/fonc.2024.1414766. eCollection 2024.
The objective of this investigation was to elucidate the key active compounds and molecular mechanisms underlying the therapeutic potential of airpotato yam rhizome (AYR) in colorectal cancer (CRC) treatment.
By utilizing network pharmacology and molecular docking, key targets and signaling pathways of AYR against CRC were predicted and subsequently validated in cellular and mouse xenograft models.
This study initially predicted that quercetin was the primary compound in AYR that might have potential efficacy against CRC and that EGFR and AKT1 could be the main targets of AYR, with the EGF/EGFR-induced PI3K/AKT signaling pathway potentially playing a crucial role in the anti-CRC effects of AYR. Molecular docking analysis further indicated a strong binding affinity between quercetin and EGFR, primarily through hydrogen bonds. Additionally, the AYR-derived drug-containing serum was found to inhibit the PI3K/AKT signaling pathway, as demonstrated by decreased levels of p-PI3K, p-AKT, and BCL2, which ultimately led to enhanced apoptosis of HCT116 and HT29 cells. The potential antitumor effects of AYR were investigated in nude mouse xenograft models of human HCT116 and HT29 cells, in which AYR was found to induce tumor cell apoptosis and inhibit tumor formation.
AYR may promote CRC cell apoptosis by suppressing the PI3K/AKT signaling pathway, which provides a basis for further research on the safe and effective use of AYR for the treatment of CRC.
本研究旨在阐明薯蓣根茎（AYR）在结直肠癌（CRC）治疗中的关键活性成分及分子机制。
利用网络药理学和分子对接技术，预测AYR抗CRC的关键靶点和信号通路，并随后在细胞和小鼠异种移植模型中进行验证。
本研究初步预测槲皮素是AYR中可能对CRC具有潜在疗效的主要化合物，EGFR和AKT1可能是AYR的主要靶点，EGF/EGFR诱导的PI3K/AKT信号通路可能在AYR的抗CRC作用中发挥关键作用。分子对接分析进一步表明槲皮素与EGFR之间具有很强的结合亲和力，主要通过氢键结合。此外，发现含AYR的药物血清可抑制PI3K/AKT信号通路，表现为p-PI3K、p-AKT和BCL2水平降低，最终导致HCT116和HT29细胞凋亡增加。在人HCT116和HT29细胞的裸鼠异种移植模型中研究了AYR的潜在抗肿瘤作用，发现AYR可诱导肿瘤细胞凋亡并抑制肿瘤形成。
AYR可能通过抑制PI3K/AKT信号通路促进CRC细胞凋亡，这为进一步研究AYR安全有效地用于CRC治疗提供了依据。
