Division of Neurosurgery, Department of Surgery, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan.
Department of Surgery, School of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.
Biomed Res Int. 2021 Mar 8;2021:5552226. doi: 10.1155/2021/5552226. eCollection 2021.
Glioblastoma multiforme (GBM) is the most common malignant brain tumor in the world. Despite advances in surgical resection, radiotherapy, and chemotherapy, GBM continues to have a poor overall survival. CDDO (2-cyano-3,12-dioxoolean-1,9-dien-28-oic acid), a synthetic triterpenoid, is an Nrf2 activator used to inhibit proliferation and induce differentiation and apoptosis in various cancer cells. One new trifluoroethylamide derivative of CDDO, RTA 404, has been found to have increased ability to cross the blood-brain barrier. However, it is not clear what effect it may have on tumorigenesis in GBM.
This in vitro study evaluated the effects of RTA 404 on GBM cells. To do this, we treated GBM840 and U87 MG cell lines with RTA 404 and assessed apoptosis, cell cycle, cell locomotion, and senescence. DNA content and induction of apoptosis were analyzed by flow cytometry and protein expression by Western blot analysis.
RTA 404 significantly inhibited the proliferation of tumor cells at concentrations higher than 100 nM ( < 0.05) and reduced their locomotion ability. In addition, treatment with RTA 404 led to an accumulation of RTA 404-treated / phase cells and apoptosis. An analysis of the p21/AKT expression suggested that RTA 404 may not only help prevent brain cancer but it may also exert antitumor activities in established GBM cells.
RTA404 can inhibit proliferation, cell locomotion, cell cycle progression, and induce apoptosis in GBM cells in vitro, possibly through its inhibition of N-cadherin and E-cadherin expression via its inhibition of the AKT pathway.
多形性胶质母细胞瘤（GBM）是世界上最常见的恶性脑肿瘤。尽管手术切除、放疗和化疗取得了进展，但 GBM 的总体生存率仍然很差。CDDO（2-氰基-3,12-二氧代-1,9-二烯-28-酸）是一种合成三萜，是一种 Nrf2 激活剂，用于抑制各种癌细胞的增殖并诱导分化和凋亡。一种 CDDO 的新三氟乙酰胺衍生物 RTA 404 已被发现具有增强穿过血脑屏障的能力。然而，尚不清楚它对 GBM 中的肿瘤发生可能有何影响。
这项体外研究评估了 RTA 404 对 GBM 细胞的影响。为此，我们用 RTA 404 处理 GBM840 和 U87 MG 细胞系，并评估细胞凋亡、细胞周期、细胞运动和衰老。通过流式细胞术分析 DNA 含量和诱导的细胞凋亡，通过 Western blot 分析蛋白表达。
RTA 404 在浓度高于 100 nM（<0.05）时可显著抑制肿瘤细胞的增殖并降低其运动能力。此外，RTA 404 处理导致 RTA 404 处理的 / 期细胞和凋亡的积累。对 p21/AKT 表达的分析表明，RTA 404 不仅有助于预防脑癌，而且可能在已建立的 GBM 细胞中发挥抗肿瘤活性。
RTA404 可在体外抑制 GBM 细胞的增殖、细胞运动、细胞周期进程并诱导细胞凋亡，可能通过抑制 AKT 通路抑制 N-钙黏蛋白和 E-钙黏蛋白的表达。
