尼罗替尼应用于1型神经纤维瘤病相关肿瘤的体外研究

Application of nilotinib to neurofibromatosis type 1-associated tumors in vitro

目的通过体外试验研究尼罗替尼（Nilotinib）对丛状神经纤维瘤（PNF）培养的Schwann细胞和恶性周围神经鞘瘤（MPNST）细胞生长特性的影响。方法利用手术切除的PNF组织培养Schwann细胞和MPNST细胞,然后用不同浓度的尼罗替尼进行处理,测定细胞增殖、活力、凋亡和胞外胶原酶活性,评价药物的效能。结果尼罗替尼处理后,细胞增殖和活力均下降,下降的程度与药物浓度成正比,其半数抑制浓度（IC50）为2.3~10.8μM。此外,尼罗替尼抑制Schwann细胞和MPNST细胞胶原酶表达活性,并诱导MPNST细胞凋亡。结论尼罗替尼在体外可有效抑制PNF肿瘤细胞和MPNST细胞的增殖和活力,促进MPNST细胞凋亡,值得进一步开展体内试验和作用机制研究。

Objective To investigate the effect of nilotinib on plexiform neurofibroma （PNF）-derived Schwann cells and malignant peripheral nerve sheath tumor（MPNST） cells in vitro. Methods The Schwann cells cultured from 10 PNF tissues and 3 established MPNST cell lines were treated by nilotinib with different concentrations. Cell proliferation, viability, apoptosis and eollagenase activity were detected to evaluate drug efficacy. Results Nilotinib treatment led to decreased cell proliferation and viability with 50% inhibitory concentration（ ICso ）varying from 2. 3 to 10. 8 p,M. In addition, nilotinib induced MPNST cell apeptosis and suppressed collagenase activity. Conclusion Nilotinib is able to inhibit proliferation and viability of PNF-derived Schwann cells and MPNST cells in vitro. It is worth performing further in vivo studies and the researches underlying mechanisms of the effects.