Department of Neurosurgery, Shenzhen Second People's Hospital, The First Affiliated Hospital of Shenzhen University Health Science Center, Shenzhen, Guangdong 518035, P.R. China.
Department of Otolaryngology Head and Neck Surgery, The First Affiliated Hospital of Sun Yat‑sen University, Guangzhou, Guangdong 510080, P.R. China.
Int J Mol Med. 2021 May;47(5). doi: 10.3892/ijmm.2021.4900. Epub 2021 Mar 2.
There is a growing evidence that Fyn kinase is upregulated in glioblastoma multiforme (GBM), where it plays a key role in tumor proliferation and invasion. In the present study, the antitumor effects of rosmarinic acid (RA), a Fyn inhibitor, were explored in human‑derived U251 and U343 glioma cell lines. These cells were treated with various concentrations of RA to determine its effects on proliferation, migration, invasion, apoptosis, and gene and protein expression levels. The CCK‑8 assay revealed that RA significantly suppressed cell viability of U251 and U343 cells. Furthermore, RA significantly reduced proliferation rates, inhibited migration and invasion, and decreased the expression levels of invasion‑related factors, such as matrix metalloproteinase (MMP)‑2 and MMP‑9. TUNEL staining revealed that RA resulted in a dose‑dependent increase of U251 and U343 cell apoptosis. In line with this finding, the expression of apoptosis suppressor protein Bcl‑2 was downregulated and that of the pro‑apoptotic proteins Bax and cleaved caspase‑3 was increased. In addition, it was revealed that the phosphatidylinositol 3‑kinase (PI3K)/Akt/nuclear factor‑κB (NF‑κB) signaling pathway was involved in RA‑induced cytotoxicity in U251 and U343 cells. Collectively, the present study suggested RA as a drug candidate for the treatment of GBM.
越来越多的证据表明，原花青素在多形性胶质母细胞瘤（GBM）中上调，在肿瘤增殖和侵袭中发挥关键作用。在本研究中，研究了原花青素（RA）作为一种芬尼激酶抑制剂对人源性 U251 和 U343 神经胶质瘤细胞系的抗肿瘤作用。用不同浓度的 RA 处理这些细胞，以确定其对增殖、迁移、侵袭、凋亡以及基因和蛋白表达水平的影响。CCK-8 检测结果显示，RA 显著抑制 U251 和 U343 细胞的活力。此外，RA 显著降低了增殖率，抑制了迁移和侵袭，并降低了侵袭相关因子（如基质金属蛋白酶（MMP）-2 和 MMP-9）的表达水平。TUNEL 染色显示，RA 导致 U251 和 U343 细胞凋亡呈剂量依赖性增加。与此一致的是，凋亡抑制蛋白 Bcl-2 的表达下调，促凋亡蛋白 Bax 和 cleaved caspase-3 的表达增加。此外，还发现磷脂酰肌醇 3-激酶（PI3K）/Akt/核因子-κB（NF-κB）信号通路参与了 RA 诱导的 U251 和 U343 细胞毒性。综上所述，本研究提示 RA 可能是治疗 GBM 的候选药物。
