Pang Wenwen, Li Xiang, Yan Suying, Zhang Junshi, Wu Ping, Yu Haiyang, Zhang Bowei, Zhang Chunze
Department of Clinical Laboratory, Tianjin Union Medical Center, Nankai University, Tianjin 300071, China.
Tianjin Integrative Traditional Chinese and Western Medicine Oncology Institute, Tianjin 300121, China.
Molecules. 2025 Sep 5;30(17):3634. doi: 10.3390/molecules30173634.
Colorectal cancer (CRC) is the third most common cancer worldwide, with liver metastasis being the leading cause of mortality. De novo fatty acid synthesis plays a critical role in CRC progression and metastasis. Bufalin, a cardiotonic steroid isolated from toad skin, has demonstrated anticancer activity in multiple preclinical models. However, the mechanisms underlying its suppression of CRC metastasis and modulation of fatty acid synthesis remain to be elucidated.
The effects of bufalin on CRC cell proliferation, migration, and apoptosis were assessed via colony formation, wound healing, and flow cytometry assays. Transcriptome analysis identified bufalin-affected pathways, with changes in gene and protein expression. FASN protein levels were quantified using ELISA.
Bufalin inhibited proliferation and migration of CRC cells and induced the apoptosis of LoVo and HCT8 cells. Transcriptome analysis highlighted lipid metabolism pathways as potential mediators of bufalin's anti-metastatic activity. Notably, bufalin reduced the expression of fatty acid synthase (FASN) and suppressed CRC metastasis. In vivo experiments demonstrated that bufalin attenuated CRC progression and liver metastasis by inhibiting de novo fatty acid synthesis through the PI3K/AKT-mediated SREBP1/FASN pathway.
Bufalin inhibits de novo fatty acid synthesis via the PI3K/AKT-mediated SREBP1/FASN pathway, suppressing CRC progression and liver metastasis.
结直肠癌（CRC）是全球第三大常见癌症，肝转移是主要死亡原因。脂肪酸从头合成在CRC进展和转移中起关键作用。蟾毒灵是一种从蟾蜍皮肤中分离出的强心甾体，已在多种临床前模型中显示出抗癌活性。然而，其抑制CRC转移和调节脂肪酸合成的潜在机制仍有待阐明。
通过集落形成、伤口愈合和流式细胞术检测评估蟾毒灵对CRC细胞增殖、迁移和凋亡的影响。转录组分析确定了受蟾毒灵影响的途径以及基因和蛋白质表达的变化。使用酶联免疫吸附测定法定量FASN蛋白水平。
蟾毒灵抑制CRC细胞的增殖和迁移，并诱导LoVo和HCT8细胞凋亡。转录组分析突出了脂质代谢途径作为蟾毒灵抗转移活性的潜在介质。值得注意的是，蟾毒灵降低了脂肪酸合酶（FASN）的表达并抑制了CRC转移。体内实验表明，蟾毒灵通过PI3K/AKT介导的SREBP1/FASN途径抑制脂肪酸从头合成，从而减轻CRC进展和肝转移。
蟾毒灵通过PI3K/AKT介导的SREBP1/FASN途径抑制脂肪酸从头合成，从而抑制CRC进展和肝转移。
