局部分泌的血管抑素K（1—3）蛋白抑制人脑胶质瘤生长的实验研究

目的 探讨局部分泌血管抑素Ｋ（１￣３）蛋白〔ａｎｇｉｏｓｔａｔｉｎ Ｋ（１￣３），ＡＫ（１￣３）〕治疗人脑胶质瘤的可行性。方法 构建ＡＫ（１￣３０基因的真核表达载体ｐｃＤＮＡ－ＳＡＫ（１￣３），经脂质体法将该载体转染入人脑胶质瘤细胞ＳＨＧ４４、行Ｇ４１８筛选。用电镜和流式细胞仪测定转染细胞的生物学性状，以内皮细胞抑制实验和免疫荧光实验检测该细胞表达的ＡＫ（１￣３）蛋白。应用裸鼠皮下致瘤性实验，结合

Inhibition of human glioma growth in nude mice by local secretion of angiostatin K(1-3)

OBJECTIVE: To discuss the feasibility of human glioma therapy by the local secretion of angiostatin K(1-3)AK(1-3)]. METHOD: AK(1-3) cDNA with secretive signal was inserted into polylinker sites of eukaryotic expression vector pcDNA3 to construct pcDNA-SAK(1-3); The vector was transfected into human glioma SHG44 cells by lipofectamine and the positive clone was screened by G418. The biological characters of glioma cells were examined with electron microscopy and FCM. The activity of AK(1-3) protein expressed by the SHG44 cells was examined by the endotheliocyte inhibition assay and immunofluorescence assay. When the tumor cells were implanted into nude mice, the tumor necrosis and micrangium was calculated by immunohistochemistry and electron microscopy in order to determine the influence of AK(1-3) protein to the human glioma growth. RESULTS: The pcDNA-SAK(1-3) vector was successfully constructed and transfected into glioma cells that could express AK(1-3) protein. The tumorigenesis and angiogenesis of glioma cells in nude mice were greatly reduced (tumour end volume, experiment group 170 mm3, control group 8 120 mm3, P < 0.01; Blood vessel counting, experimental group 5.4, control group 12.2, P < 0.01). CONCLUSION: The human glioma angiogenesis and growth were inhibited by the local secretion of AK(1-3). It can be further used in the treatment of other solid tumors.