癌症研究
替莫唑胺
癌症干细胞
癌细胞
生物
干细胞
胶质母细胞瘤
癌症
化学
细胞生物学
遗传学
作者
Kai-Ming Chang,Chih Ta Huang,Todd Hsu,Che Chia Hsu,Jr Jiun Liu,Cheng Keng Chuang,Jan Jong Hung,Wen Chang Chang,Kelvin K. Tsai,Jian Ying Chuang
标识
DOI:10.1016/j.bbrc.2017.09.095
摘要
It has been suggested that stress stimuli from the microenvironment maintain a subset of tumor cells with stem-like properties, including drug resistance. Here, we investigate whether Sp1, a stress-responsive factor, regulates stemness gene expression and if its inhibition sensitizes cancer cells to chemotherapy. Hydrogen peroxide- and serum deprivation-induced stresses were performed in glioblastoma (GBM) cells and patient-derived cells, and the effect of the Sp1 inhibitor mithramycin A (MA) on these stress-induced stem cells and temozolomide (TMZ)-resistant cells was evaluated. Sp1 and stemness genes were not commonly overexpressed in clinical GBM samples. However, their expression was highly induced by stress stimuli. Using MA, we demonstrated Sp1 as a critical stemness-related transcriptional factor protecting GBM cells against stress- and TMZ-induced death. Thus, Sp1 inhibition may prevent recurrence of malignant cells persisting after primary therapy.
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