BMP4对胶质瘤干细胞恶性增殖的影响

Effect of BMP4 on malignant proliferation of glioblastoma

目的探讨骨形态发生蛋白4(BMP4)对脑肿瘤干细胞(BTSC)体内外增殖能力的影响。方法神经球培养法分离胶质母细胞瘤(GBM)来源的BTSCs,给予外源BMP4刺激后,集落形成实验(CFU)观察BTSCs克隆形成能力、四甲基偶氮唑盐比色(MTT)法检测BTSCs的增殖能力变化;并利用立体定向技术制备裸鼠脑内BTSCs移植瘤模型,检测BMP4对BTSCs在裸鼠颅内成瘤性影响。结果外源BMP4刺激可以明显抑制BTSCs的克隆形成能力,并明显减低BTSCs的体外增殖能力。裸鼠体内实验结果显示,BMP4的预刺激,可以使BTSCs在移植入裸鼠颅内4 w后,无明显肿瘤生长迹象,仅见沿针道走行的移植细胞。结论外源BMP4对BTSCs的体内、外增殖具有明显的抑制作用,这一特性可被用于GBM的生物靶向治疗。

Objective To study the effects of bone morphogenetic protein 4 （BMP4） on the proliferation of brain tumour stem ceils （BTSCs）. Methods Human BTSCs were obtained by neurosphere culture. Colony-formation units （CYU） and methye thiazolye telrazlium （MIT） assay were used to evaluate the effects of BMP4 on colonality and proliferation capacity. Futhermore, the effects of BMP4 on the tumorigenicity were studied in nude mice model. Results BMP4 could significantly reduce the colonality and proliferation capacity in vitro, inhibited the ttmlorigenicity and invasion of BTSCs in the brain of nude mice model, and also could prolong the survival time of nude mice. Conclusion BMP4 could inhibit the malignant proliferation in vitro and in vivo, and could be used in the targeted therapy of GBM in the future.