TCM Department, The Affiliated Hospital of Yangzhou University, Yangzhou University, No. 136, Jiangyang Middle Road, Yangzhou, 225001, Jiangsu, People's Republic of China.
Institute of Translational Medicine, Medical College, Yangzhou University, Yangzhou, 225001, People's Republic of China.
J Nat Med. 2024 Jan;78(1):100-113. doi: 10.1007/s11418-023-01748-0. Epub 2023 Oct 10.
Cancer stem cells (CSCs) are the primary source of tumor recurrence and chemoresistance, which complicates tumor treatment and has a significant impact on poor patient prognosis. Therefore, the discovery of inhibitors that specifically target CSCs is warranted. Previous research has established that the TGF-β/Smad signaling pathway is critical for the maintenance of CSCs phenotype, thus facilitating CSCs transformation. In this regard, Celastrus orbiculatus ethyl acetate extract (COE) was shown to exert anticancer properties; however, its therapeutic impact on gastric cancer stem cells (GCSCs) remains unknown. We here demonstrate that COE displayed a strong inhibitory effect on GCSCs growth and CSCs markers. Moreover, COE was shown to efficiently inhibit the development of tumor spheres and accelerate GCSCs apoptosis. Mechanistically, we established that COE could suppress the stemness phenotype of GCSCs by inhibiting the activity of the TGF-β/Smad signaling pathway. To summarize, our data indicate that COE suppresses the malignant biological phenotype of GCSCs via the TGF-β/Smad signaling pathway. These findings shed new light on the anticancer properties of COE and suggest new strategies for the development of efficient GCSCs therapeutics.
癌症干细胞 (CSCs) 是肿瘤复发和化疗耐药的主要来源，这使得肿瘤治疗变得复杂，并对患者预后产生重大影响。因此，有必要发现专门针对 CSCs 的抑制剂。先前的研究已经证实，TGF-β/Smad 信号通路对于维持 CSCs 表型至关重要，从而促进 CSCs 的转化。在这方面，南蛇藤乙酸乙酯提取物 (COE) 已被证明具有抗癌特性；然而，其对胃癌干细胞 (GCSCs) 的治疗作用尚不清楚。我们在这里证明，COE 对 GCSCs 的生长和 CSCs 标志物具有强烈的抑制作用。此外，COE 被证明可以有效地抑制肿瘤球体的发育并加速 GCSCs 凋亡。在机制上，我们确定 COE 可以通过抑制 TGF-β/Smad 信号通路来抑制 GCSCs 的干性表型。总之，我们的数据表明，COE 通过 TGF-β/Smad 信号通路抑制 GCSCs 的恶性生物学表型。这些发现为 COE 的抗癌特性提供了新的线索，并为开发有效的 GCSCs 治疗策略提供了新的思路。
