Department of Integrated Therapy, Fudan University Shanghai Cancer Center, Shanghai 200032, China.
Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032, China, and.
Acta Biochim Biophys Sin (Shanghai). 2020 Sep 8;52(9):1007-1015. doi: 10.1093/abbs/gmaa075.
Vasculogenic mimicry (VM) refers to a new tubular network of the blood supply system with abundant extracellular matrix. VM is similar to capillaries but does not involve endothelial cells. As a traditional herbal medicine commonly used in China, baicalein possesses anti-inflammatory and lipoxygenase activities. However, the effects of baicalein on the process of VM formation in non-small cell lung cancer (NSCLC) and the underlying mechanisms have remained poorly understood. In this study, baicalein was found to inhibit the viability and motility of A549 cells and induced the breakage of the cytoskeletal actin filament network. In addition, baicalein significantly decreased the formation of VM and downregulated the expressions of VM-associated factors, such as VE-cadherin, EphA2, MMP14, MMP2, MMP9, PI3K and LAMC2, similar to the effects of ROCK inhibitors. Indeed, baicalein inhibited RhoA/ROCK expression in vitro and in vivo, suggesting the underlying mechanisms of reduced VM formation. Collectively, baicalein suppressed the formation of VM in NSCLC by targeting the RhoA/ROCK signaling pathway, indicating that baicalein might serve as an emerging drug for NSCLC.
血管生成拟态（VM）是指富含细胞外基质的新的血液供应系统的管状网络。VM 类似于毛细血管，但不涉及内皮细胞。作为中国常用的传统草药，黄芩素具有抗炎和脂氧合酶活性。然而，黄芩素对非小细胞肺癌（NSCLC）中 VM 形成过程的影响及其潜在机制仍知之甚少。本研究发现黄芩素可抑制 A549 细胞的活力和迁移，并诱导细胞骨架肌动蛋白丝网络的断裂。此外，黄芩素显著减少 VM 的形成，并下调 VM 相关因子的表达，如 VE-钙黏蛋白、EphA2、MMP14、MMP2、MMP9、PI3K 和 LAMC2，与 ROCK 抑制剂的作用相似。事实上，黄芩素在体外和体内抑制 RhoA/ROCK 的表达，提示了减少 VM 形成的潜在机制。总之，黄芩素通过靶向 RhoA/ROCK 信号通路抑制 NSCLC 中 VM 的形成，表明黄芩素可能成为 NSCLC 的一种新兴药物。
