Neurosurgery, The Affiliated Hospital of Qingdao University, Qingdao, 266000, Shandong, China.
Neurosurgery, Linyi Traditional Chinese Medical Hospital, Linyi, 276000, Shandong, China.
Sci Rep. 2023 Sep 19;13(1):15484. doi: 10.1038/s41598-023-41421-w.
The purpose of this study was to explore the role of coixendide (Coix) combine with temozolomide (TMZ) in the treatment of Glioblastoma (GBM) and explore its possible mechanism. CCK-8 was used to determine the inhibitory rate of Coix group, TMZ group and drug combination group on GBM cells, and the combination index (CI) was calculated to determine whether they had synergistic effect. Then RNA was extracted from each group, transcriptome sequencing was performed, and differentially expressed genes (DEGs) were identified. The possible mechanism was analyzed by GO enrichment analysis and KEGG enrichment analysis. The CI of Coix and TMZ indicating a synergistic effect when TMZ concentration is 0.1 mg/ml and Coix concentration is 2 mg/ml. Transcriptome sequencing analysis showed that interferon (IFN) related genes were down-regulated by Coix and up-regulated by TMZ and combined drugs, however, the up-regulation induced by combined drugs was less than that of TMZ. Besides IFN related genes, cholesterol metabolism pathway were also been regulated. Coix and TMZ have synergistic effects in the treatment of GBM at certain doses. RNA-Seq results suggested that the abnormal on genetic materials caused by DNA damage induced by TMZ treatment can be sensed by IFN related genes and activates antiviral IFN signaling, causing the activation of repairing mechanism and drug resistance. Coix inhibits IFN related genes, thereby inhibits drug resistance of TMZ. In addition, the activation of ferroptosis and the regulation of DEGs in cholesterol metabolism pathway were also contributed to the synergistic effects of Coix and TMZ.
本研究旨在探讨薏苡仁（Coix）联合替莫唑胺（TMZ）治疗胶质母细胞瘤（GBM）的作用及其可能的机制。采用 CCK-8 法检测 Coix 组、TMZ 组及药物联合组对 GBM 细胞的抑制率，计算联合指数（CI）判断是否具有协同作用。然后从各组提取 RNA，进行转录组测序，筛选差异表达基因（DEGs）。通过 GO 富集分析和 KEGG 富集分析对可能的作用机制进行分析。Coix 与 TMZ 的 CI 提示当 TMZ 浓度为 0.1mg/ml，Coix 浓度为 2mg/ml 时具有协同作用。转录组测序分析表明，Coix 下调 IFN 相关基因，TMZ 及联合药物上调 IFN 相关基因，但联合药物上调幅度小于 TMZ。除 IFN 相关基因外，胆固醇代谢途径也受到调控。在一定剂量下，Coix 和 TMZ 对 GBM 具有协同作用。RNA-Seq 结果提示，TMZ 治疗引起的 DNA 损伤所导致的遗传物质异常可被 IFN 相关基因感知，并激活抗病毒 IFN 信号，引起修复机制的激活和耐药。Coix 抑制 IFN 相关基因，从而抑制 TMZ 的耐药性。此外，铁死亡的激活和胆固醇代谢途径中 DEGs 的调控也有助于 Coix 和 TMZ 的协同作用。
