血管生成抑制剂TNP-470对人恶性胶质瘤细胞系SHG-44及其移植瘤生长的影响

目的：观察TNP－470对人恶性胶质瘤细胞系SHG－44体内和体外生长的影响。方法：采用MTT法、软琼脂克隆法、流式细胞仪、光镜和透射电镜技术观察SHG－44细胞体内外增殖、克隆形成、细胞周期和形态学变化及异种移植瘤生长情况。结果：20－2000ng/mlTNP－470可显著抑制SHG－44细胞体外增殖，克隆形成率显著降低，G0／G1期细胞明显增多，S、G2／M期细胞减少。彩和30mg/kg体重TNP－470隔日皮下注射后，移植瘤体积缩小、重量显著减轻，组织出现明显调亡细胞和坏死。结论：TNP－470对SHG-44细胞的生长抑制作用与其调控细胞周期和诱导细胞凋亡相关，提示TNP－470作为一种血管生成抑制剂对胶质瘤细胞生长也具有直接抑制作用。

Inhibitory effects of angiogenesis inhibitor TNP-470 on growth of a human malignant glioma cell line SHG-44 and its xenografted tumor

Objective　To investigate the effects of TNP-470 on the growth of a human malignant glioma cell line SHG-44 in vivo and in vitro. Methods　The colorimetric MTT assay, soft agar culture, flow cytometry，light and electron microscopy were used to determine the proliferation, the cloning efficiency, cell cycle and the morphological changes of SHG-44 cells as well as the growth of its xenografted tumor. Results　TNP-470 (20～2 000 ng/ml) significantly inhibited the proliferation of SHG-44 cells in vitro (the 50% inhibitory concentration was 200 ng/ml). Cloning efficiency reduced obviously. The number of cells in G0/G1 phase increased, while that in S, G2/M phases decreased significantly. Weight and volume of xenografted tumors treated with TNP-470 (30 mg/kg, injected subcutaneously every other day) reduced notably. Furthermore, there were necrotic area and apoptosis in the tumor. No severe side effect of TNP-470 was found in this study. Conclusion　The inhibitory effect of TNP-470 on the growth of SHG-44 cells correlates with its functions of regulating cell cycle and inducing apoptosis, which suggests that the angiogenesis inhibitor TNP-470 has strong inhibitory effect on human malignant gliomas.