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沙利霉素通过选择性抑制胶质瘤起始细胞来抑制胶质瘤干细胞的肿瘤生长。

Salinomycin inhibits the tumor growth of glioma stem cells by selectively suppressing glioma-initiating cells.

作者信息

Chen Tunan, Yi Liang, Li Fei, Hu Rong, Hu Shengli, Yin Yi, Lan Chuan, Li Zhao, Fu Chuhua, Cao Liu, Chen Zhi, Xian Jishu, Feng Hua

机构信息

Department of Neurosurgery, Southwest Hospital, Chongqing 400038, P.R. China.

Department of Neurosurgery, Daping Hospital, Chongqing 400042, P.R. China.

出版信息

Mol Med Rep. 2015 Apr;11(4):2407-12. doi: 10.3892/mmr.2014.3027. Epub 2014 Dec 1.

Abstract

Glioma‑initiating cells are a small population of cells that have the ability to undergo self‑renewal and initiate tumorigenesis. In the present study, the potential role of salinomycin, a polyether antibiotic, on the suppression of glioma cell growth was investigated. GL261 glioma cells were maintained in a stem‑cell‑like status [GL261 neurospheres (GL261‑NS)] or induced for differentiation [GL261 adherent cells (GL261‑AC)]. It was demonstrated that salinomycin significantly reduced the cell viability of GL261‑NS and GL261‑AC cells in a dose‑dependent manner, with a more substantial inhibition of GL261‑NS proliferation (P<0.05). The inhibitory effect of salinomycin on cell growth was more effective than that of 1‑(4‑amino‑2‑methyl‑5‑pyrimid l)‑methyl‑3‑(2‑chloroethyl)‑3‑nitrosourea hydrochloride and vincristine (P<0.05). Salinomycin depleted GL261‑NS from tumorspheres and induced cell apoptosis. In addition, salinomycin prolonged the median survival time of glioma‑bearing mice (P<0.05). Therefore, the present study indicated that salinomycin may preferentially inhibit glioma‑initiated cell growth by inducing apoptosis, suggesting that salinomycin may provide a valuable therapeutic strategy for the treatment of malignant glioma.

摘要

胶质瘤起始细胞是一小群具有自我更新能力并能引发肿瘤发生的细胞。在本研究中,研究了聚醚抗生素沙利霉素对抑制胶质瘤细胞生长的潜在作用。GL261胶质瘤细胞维持在干细胞样状态[GL261神经球(GL261-NS)]或诱导分化[GL261贴壁细胞(GL261-AC)]。结果表明,沙利霉素以剂量依赖性方式显著降低GL261-NS和GL261-AC细胞的活力,对GL261-NS增殖的抑制作用更显著(P<0.05)。沙利霉素对细胞生长的抑制作用比盐酸1-(4-氨基-2-甲基-5-嘧啶基)-甲基-3-(2-氯乙基)-3-亚硝基脲和长春新碱更有效(P<0.05)。沙利霉素使肿瘤球中的GL261-NS减少并诱导细胞凋亡。此外,沙利霉素延长了荷胶质瘤小鼠的中位生存时间(P<0.05)。因此,本研究表明沙利霉素可能通过诱导凋亡优先抑制胶质瘤起始细胞的生长,提示沙利霉素可能为恶性胶质瘤的治疗提供一种有价值的治疗策略。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f162/4337630/132ec3a45612/MMR-11-04-2407-g00.jpg

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