Department of Neurosurgery, The Third Affiliated Hospital of Chongqing Medical University (Gener Hospital), PR China.
Department of Neurosurgery, The Affiliated Huai'an Hospital of Xuzhou Medical University and The Second People's Hospital of Huai'an, PR China.
Pathol Res Pract. 2020 Feb;216(2):152789. doi: 10.1016/j.prp.2019.152789. Epub 2019 Dec 17.
Coronarin D (CD) is one of the primary components of the Hedychium coronarium rhizomes and possesses strong anticancer effects via preventing cell growth in many cancer cells. The study was aimed to explore the molecular mechanisms underlying effects of CD on proliferation, invasion and migration of gliomas cells. Gliomas cell lines U251 was employed for detecting cells viability and proliferation by Cell Counting Kit-8 assay and colony formation assay. In addition, scratch wound healing and transwell assays were performed for the analysis of U251 cells invasion and migration respectively. Furthermore, the expression of p-Akt/Akt, p-p38/p38, p-ERK/ERK, p-JNK/JNK, p-STAT3/STAT3, cyclinE, cyclinD1, CTGF, MMP-2 and MMP-9 were measured by Western blotting. CD could suppress proliferation, invasion and migration of glioma cells and induced reduction of cyclinE, cyclinD1, CTGF, MMP-2 and MMP-9 expression via activating JNK signaling pathway. CD treatment suppressed expression of p-AKT, p38, and ERK and elevated expression of p-JNK in concentration- and time-dependent manners. Moreover, CD significantly induced reduction of phosphorylated STAT3 expression. Exposure of cells to the JNK-specific inhibitor SP600125 reduced the cytotoxicity effects of CD, combination of CD and SP600125 corrected overexpression of phosphorylated JNK and reduction of phosphorylated STAT3. Pretreatment of SP600125 also improves gliomas cells viability and invasion. The results revealed that CD may remarkably suppress gliomas cell growth through JNK and STAT3 signaling. In present study, these findings revealed that CD induces suppression of cell viability in gliomas cells and possesses therapeutic effect on gliomas.
冠状菌素 D(CD)是姜黄根茎的主要成分之一,通过防止多种癌细胞的细胞生长,具有很强的抗癌作用。本研究旨在探讨 CD 对神经胶质瘤细胞增殖、侵袭和迁移的影响的分子机制。采用细胞计数试剂盒-8 检测法和集落形成实验检测 U251 神经胶质瘤细胞活力和增殖;划痕愈合实验和 Transwell 实验分别用于分析 U251 细胞的侵袭和迁移。此外,通过 Western blot 检测 p-Akt/Akt、p-p38/p38、p-ERK/ERK、p-JNK/JNK、p-STAT3/STAT3、cyclinE、cyclinD1、CTGF、MMP-2 和 MMP-9 的表达。CD 可抑制神经胶质瘤细胞的增殖、侵袭和迁移,并通过激活 JNK 信号通路诱导 cyclinE、cyclinD1、CTGF、MMP-2 和 MMP-9 表达减少。CD 处理呈浓度和时间依赖性地抑制 p-AKT、p38 和 ERK 的表达,并升高 p-JNK 的表达。此外,CD 显著诱导磷酸化 STAT3 表达减少。用 JNK 特异性抑制剂 SP600125 处理细胞可降低 CD 的细胞毒性作用,CD 和 SP600125 的联合处理可纠正磷酸化 JNK 的过表达和磷酸化 STAT3 的减少。SP600125 的预处理也可提高神经胶质瘤细胞的活力和侵袭能力。结果表明,CD 可能通过 JNK 和 STAT3 信号显著抑制神经胶质瘤细胞的生长。本研究表明,CD 可显著抑制神经胶质瘤细胞的活力,并对神经胶质瘤具有治疗作用。