Paeoniflorin elicits the anti-proliferative effects on glioma cell via targeting translocator protein 18 KDa
Paeoniflorin elicits the anti-proliferative effects on glioma cell via targeting translocator protein 18 KDa
复制标题
芍药苷通过靶向易位蛋白 18 KDa 对神经胶质瘤细胞产生抗增殖作用
DOI：
10.1016/j.jphs.2020.10.004
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发表时间：
2021-01-01
影响因子：
3.5
通讯作者：
Liu, Xiao-fen
中科院分区：
文献类型：
--
作者：
Gao, Zhuo-wei;Huang, Yu-yun;Liu, Xiao-fen
芍药苷（PF）是从黄芪中分离得到的天然化合物，对多种人类肿瘤具有抗肿瘤作用，其中神经胶质瘤是中枢神经系统的重要肿瘤之一。转运蛋白18 KDa（TSPO）与胶质瘤的发病机制密切相关。然而，PF在胶质瘤TSPO和神经甾体类化合物生物合成中的调节作用尚不清楚。本研究采用体外培养的胶质瘤细胞（U87和U251），观察PF与TSPO的结合情况。结果表明，PF与TSPO配体PK 11195的IC 50无显著性差异。此外，PF在体外对胶质瘤细胞具有抗增殖作用，在12.5 - 100 μ M范围内呈剂量依赖性抑制。与PK 11195的作用一致，PF（25和50 μ M）诱导孕酮、别孕烯醇酮以及TSPO mRNA水平降低。此外，PF处理以及PK 11195给药显著抑制了U87细胞衍生的异种移植小鼠模型。这些结果表明，PF发挥其抗肿瘤作用与胶质瘤细胞中的TSPO和神经甾体生物合成相关，可能是一种有希望的胶质瘤治疗剂。(C)2020年，任作家。Elsevier B. V.代表日本药理学会制作和主办。
As a natural compound isolated from Paeoniae radix, Paeoniflorin (PF) has been shown the antitumor effects in various types of human cancers including glioma, which is one of the serious tumors in central nervous system. Translocator protein 18 KDa (TSPO) has been shown to be relevant to the glioma aetiology. However, the regulation of PF in TSPO and neurosteriods biosynthesis on glioma is still unclear. In the present study, the glioma cell (U87 and U251) were cultured and used to quantify the bindings of PF on TSPO. Results indicated that there was not significant different between IC50 of PF and TSPO ligand PK11195. Moreover, PF exerted the anti-proliferative effects in glioma cell with a dose dependent inhibition from 12.5 to 100 mu M in vitro. Consistent with the effects of PK11195, lowered levels on progesterone, allopregnanolone, as well as TSPO mRNA were induced by PF (25 and 50 mu M). Furthermore, a xenograft mouse model with U87 cell-derived was significant inhibited by PF treatment, as well as the PK11195 administration. These results demonstrate that PF exerts its antitumor effects associated with the TSPO and neurosteroids biosynthesis in glioma cells could be a promising therapeutic agent for glioma therapy. (C) 2020 The Authors. Production and hosting by Elsevier B.V. on behalf of Japanese Pharmacological Society.