多形性神經膠質母細胞瘤（GBM）是常見的腦腫瘤類型之一，主要源於星狀膠質細胞。目前多形性神經膠質母細胞瘤的治療策略是綜合手術切除與放射療法及化學療法，然而在這些治療後，病人壽命延長的成功率與存活率仍然很低。抗藥性是抗癌藥物替莫唑胺（TMZ）治療多形性神經膠質母細胞瘤失敗的主要原因。因此，我們有興趣探討在多形性神經膠質母細胞瘤中癌幹細胞（GSCs）以及受替莫唑胺刺激的多形性神經膠質母細胞瘤對於先天性抗藥性與後天性抗藥性的影響。根據Oncomine數據庫分析的結果，我們發現CCAAT/enhancer binding protein delta (CEBPD)在多形性神經膠質母細胞瘤中高度表達。實驗結果證實CEBPD能夠提高幹細胞轉錄因子包括SOX2，OCT4和NANOG和藥物外排轉運蛋白ABCA1的表現，分別促成癌幹細胞的幹細胞化以及先天性抗藥性。此外，我們同時證實CEBPD會受到替莫唑胺的誘導，並且參與在替莫唑胺誘導SOX2，OCT4，NANOG和ABCA1的過程中。總而言之，我們提供一個CEBPD參與在多形性神經膠質母細胞瘤中及其連接先天性抗藥性和後天性抗藥性的新穎角色。

Glioblastoma (GBM) is one of the brain tumor types and arises from astrocytes. Currently, administrations of anticancer drug and radiation therapy are the most common strategies used in GBM therapy. However, the rate of successful outcome and survival of prolong time remain very low following these treatments. Drug resistance is the main reason of failure therapy of anticancer drug temozolamide (TMZ) in GBM. We were interested in investigating the involvement of intrinsic and acquired resistance in glioblastoma stem cells (GSCs) of GBM and TMZ-treated GBM, respectively. Regarding to the result of Oncomine database analysis, we found that transcription factor CCAAT/enhancer binding protein delta (CEBPD) is highly expressed in GBM. We further demonstrated that CEBPD contributed to sphere formation of GSCs and intrinsic TMZ resistance via upregulating stem cell transcription factors, including SOX2, OCT4, and NANOG and drug efflux transporter ABCA1. In addition, we demonstrated that CEBPD is responsive to TMZ and was also involved in TMZ-induced SOX2, OCT4, NANOG and ABCA1 in TMZ-treated GBM cells. Taken together, we revealed a new insight of CEBPD involvement in GBM stemness and its link connecting intrinsic and acquired resistance.

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