Anti-tumor effects of progesterone in human glioblastoma multiforme: Role of PI3K/Akt/mTOR signaling
Anti-tumor effects of progesterone in human glioblastoma multiforme: Role of PI3K/Akt/mTOR signaling
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DOI：
10.1016/j.jsbmb.2014.04.007
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发表时间：
2015-02-01
影响因子：
4.1
通讯作者：
Stein, Donald G.
中科院分区：
文献类型：
--
作者：
Atif, Fahim;Yousuf, Seema;Stein, Donald G.
多形性胶质母细胞瘤（GBM）是一种侵袭性原发性脑肿瘤，尽管进行了手术切除、放射治疗和标准治疗化疗，患者的平均生存期为13-15个月。我们研究了孕激素（P4）对四种不同遗传的细胞系（U87 MG，U87 dEGFR，U118 MG，LN-229）在体外和U87 MG皮下异种移植小鼠模型中的人GBM生长的化疗作用。在高浓度（20，40，和80 μ M），P4显着（P < 0.05），在所有细胞系的肿瘤细胞活力下降，LN-229除外。P4受体拮抗剂RU 468不能阻断这种作用。相反，在低生理浓度（0.1，1，和5 μ M）P4显示在所有细胞系的增殖作用，这是由RU 486阻断。在裸小鼠中，P4（100和200 mg/l）
Glioblastoma multiforme (GBM) is an aggressive primary brain tumor with a mean patient survival of 13-15 months despite surgical resection, radiation therapy and standard-of-care chemotherapy. We investigated the chemotherapeutic effects of the hormone progesterone (P4) on the growth of human GBM in four genetically different cell lines (U87MG, U87dEGFR, U118MG, LN-229) in vitro and in a U87MG subcutaneous xenograft mouse model. At high concentrations (20, 40, and 80 mu M), P4 significantly (P < 0.05) decreased tumor cell viability in all cell lines except LN-229. This effect was not blocked by the P4 receptor antagonist RU468. Conversely, at low physiological concentrations (0.1, 1, and 5 mu M) P4 showed a proliferative effect in all cell lines which was blocked by RU486. In nude mice, P4 (100 and 200 mg/1