Zhou Li, Yan Ming-Xia, Yao Ming, Feng You-Ji
Institute of Obstetrics and Gynecology, Fudan University, Shanghai, 200011, PR China.
Ai Zheng. 2005 Nov;24(11):1312-6.
BACKGROUND & OBJECTIVE: Tumor necrosis factor-related apoptosis inducing ligand (TRAIL) can induce apoptosis in various cancer cell lines with little toxicity toward normal cells. It offers a promising therapeutic method against ovarian cancer. Endothelial progenitor cells (EPCs) could home to tumor lesion, and take part in angiogenesis. This study was to observe antitumor effect of EPCs with TRAIL gene transfection on human ovarian epithelial cancer xenografts in nude mice.
EPCs were isolated from human cord blood by magnetic bead selection, and cultured and amplified in vitro. Human ovarian epithelial cancer cell line 3AO cells were transplanted subcutaneously in immunodeficiency nude mice. EPCs were transfected with hTRAIL plasmid (TRAIL-EPCs). TRAIL-EPCs, TRAIL, or culture media IMDM (control) was injected into the mice model of 3AO xenograft by caudal vein. The changes of tumor volume were observed, and the tumor growth inhibition rate was calculated.
EPCs with TRAIL gene transfection obviously inhibited the growth of 3AO xenograft in nude mice; the tumor weight of control, TRAIL, and TRAIL-EPCs groups were (0.226 +/- 0.209) g, (0.118 +/- 0.164) g, and (0.075 +/- 0.084) g, respectively, the maximum tumor growth inhibition rate was significantly higher in TRAIL-EPCs group than in TRAIL group (66.9% vs. 48.1%, P < 0.05). HE staining showed that there were more hemorrhage and necrosis regions in TRAIL and TRAIL-EPCs groups than in control group. No severe toxic reaction was observed in the 2 groups.
Both TRAIL and TRAIL-EPCs can inhibit the growth of ovarian epithelial carcinoma xenograft in nude mice. EPCs have certain guidance effect in tumor xenografts in nude mice.
肿瘤坏死因子相关凋亡诱导配体(TRAIL)可诱导多种癌细胞系凋亡,对正常细胞毒性较小,为卵巢癌的治疗提供了一种有前景的方法。内皮祖细胞(EPCs)可归巢至肿瘤病灶并参与血管生成。本研究旨在观察转染TRAIL基因的EPCs对人卵巢上皮癌裸鼠移植瘤的抗肿瘤作用。
采用磁珠分选法从人脐血中分离EPCs,体外培养扩增。将人卵巢上皮癌细胞系3AO细胞皮下移植到免疫缺陷裸鼠体内。用hTRAIL质粒转染EPCs(TRAIL-EPCs)。将TRAIL-EPCs、TRAIL或培养基IMDM(对照)经尾静脉注射到3AO移植瘤小鼠模型中。观察肿瘤体积变化,计算肿瘤生长抑制率。
转染TRAIL基因的EPCs明显抑制裸鼠3AO移植瘤的生长;对照组、TRAIL组和TRAIL-EPCs组的肿瘤重量分别为(0.226±0.209)g、(0.118±0.164)g和(0.075±0.084)g,TRAIL-EPCs组的最大肿瘤生长抑制率明显高于TRAIL组(66.9%对48.1%,P<0.05)。HE染色显示,TRAIL组和TRAIL-EPCs组的出血和坏死区域比对照组更多。两组均未观察到严重的毒性反应。
TRAIL和TRAIL-EPCs均可抑制裸鼠卵巢上皮癌移植瘤的生长。EPCs对裸鼠肿瘤移植瘤有一定的导向作用。