肿瘤坏死因子相关凋亡配体转染骨髓干细胞后对U251胶质瘤细胞的体外靶向抗瘤作用

In vitro targeted antitumor effects of bone marrow stem cells transfected by tumor necrosis factor-related apoptosis-inducing ligand against U251 glioma cells

摘要:

目的 探究肿瘤坏死因子相关凋亡诱导配体（TRAIL）体外转染骨髓干细胞（BMSCs）后对U251脑胶质瘤细胞生长及凋亡的作用。方法 利用Transwells小室研究骨髓干细胞的肿瘤迁徙性。将携带TRAIL的质粒体外转染人骨髓干细胞，采用PCR及Western blot检测转染后BMSCs中目的基因的表达强度。将转染的BMSCs与U251细胞体外共培养，采用流式细胞仪检测转染后的BMSCs诱导U251细胞的凋亡情况。结果 BMSCs具备向肿瘤细胞的迁徙性。转染后的骨髓干细胞表达、分泌TRAIL，且干细胞凋亡情况无变化。将转染后的BMSCs与U251细胞共同培养，可明显提高U251细胞的凋亡率，BMSCs TRAIL+U251组U251细胞凋亡率明显高于对照组（P <0.05）。结论 在体外实验中，利用BMSCs肿瘤迁徙的特异性，将BMSCs作为基因载体，可提高TRAIL对U251胶质瘤细胞的靶向抑癌作用。

Abstract:

【Objective】 To study the targeted antitumor effects of bone marrow stem cells (BMSCs) transfected by tumor necrosis factor-related apoptosis--inducing ligand (TRAIL) against glioma in vitro. 【Methods】 The migration capacity of BMSCs toward glioma was investigated using Transwells inserts. The in vitro expression of target gene in transfected BMSCs was detected by PCR and Western blot. The apoptosis of U251 cells was analyzed by flow cytometry after the co-culture with the transfected BMSCs. 【Results】 First, BMSCs had the capacity of mobilizing toward tumor cells. Second, although the BMSCs expressed and secreted TRAIL, their apoptosis was unchanged. Third, the apoptosis rate of U251 cells increased significantly after the co-culture with the transfected BMSCs (P < 0.05). 【Conclusions】 Using BMSCs as gene vectors, the targeted antitumor effects of TRAIL against U251 glioma cells can be increased by the specific mobility of BMSCs towards tumor in vitro.