Department of Colorectal Surgery, The First Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang 150001, P.R. China.
Department of Ultrasonic Imaging, First Clinical Medical College, Shanxi Medical University, Taiyuan, Shanxi 030001, P.R. China.
Oncol Rep. 2021 Jan;45(1):139-150. doi: 10.3892/or.2020.7857. Epub 2020 Nov 18.
Fangchinoline (FAN), an alkaloid extracted from Stephania tetrandra, has a variety of biological and pharmacological activities, but evidence of its effects on colon adenocarcinoma (COAD) is limited. Therefore, the present study aimed to elucidate the molecular mechanisms by which FAN affects COAD. The cytotoxicity, viability and proliferation of DLD‑1 and LoVo cells were assessed in the presence of FAN using MTT and colony formation assays. The effects of FAN on apoptosis and the cell cycle in COAD cells were analysed by flow cytometry, and the migration and invasion of these cells were assessed by wound healing and Transwell experiments. Furthermore, a network pharmacological analysis was conducted to investigate the target of FAN and the results were confirmed by western blotting. In addition, a xenograft model was established in nude mice, and ultrasound imaging was used to assess the preclinical therapeutic effects of FAN in vivo. To the best of our knowledge, the results of this study provided the first evidence that FAN inhibited cellular proliferation, stemness, migration, invasion, angiogenesis and epithelial‑mesenchymal transition (EMT), and induced apoptosis and G1‑phase cell cycle arrest. Network pharmacological analysis further confirmed that FAN prevented EMT through the epidermal growth factor receptor (EGFR)‑phosphoinositide 3‑kinase (PI3K)/AKT signalling pathway. Finally, FAN significantly repressed tumour growth and promoted apoptosis in xenografts. Thus, targeting EGFR with FAN may offer a novel therapeutic approach for COAD.
防己诺林碱（FAN）是从粉防己中提取的一种生物碱，具有多种生物和药理活性，但关于其对结肠腺癌（COAD）影响的证据有限。因此，本研究旨在阐明 FAN 影响 COAD 的分子机制。采用 MTT 和集落形成实验评估 FAN 对 DLD-1 和 LoVo 细胞的细胞毒性、活力和增殖的影响。通过流式细胞术分析 FAN 对 COAD 细胞凋亡和细胞周期的影响，通过划痕愈合和 Transwell 实验评估这些细胞的迁移和侵袭能力。此外，还进行了网络药理学分析，以研究 FAN 的作用靶点，并通过 Western blot 验证结果。此外，还在裸鼠中建立了异种移植模型，并通过超声成像评估 FAN 在体内的临床前治疗效果。据我们所知，这项研究的结果首次提供了证据表明 FAN 抑制了细胞增殖、干性、迁移、侵袭、血管生成和上皮间质转化（EMT），并诱导了细胞凋亡和 G1 期细胞周期阻滞。网络药理学分析进一步证实，FAN 通过表皮生长因子受体（EGFR）-磷酸肌醇 3-激酶（PI3K）/AKT 信号通路防止 EMT。最后，FAN 显著抑制了异种移植瘤的生长并促进了凋亡。因此，用 FAN 靶向 EGFR 可能为 COAD 提供一种新的治疗方法。
