The antiangiogenic effect of thalidomide on murine liver metastases / 中华放射学杂志

ABSTRACT

Objective To investigate the morphological change of intratumoral microvessels after administration of thalidomide in the murine hepatic metastases. Methods Among 20 mice with hepatic metastases created by injection of colon-26 tumor cells into the spleen, 10 were treated with thalidomide (200 mg/kg) by intraperitoneal injection daily, the other 10 were treated with saline only by intraperitoneal injection daily. Fifteen days after inoculation of tumor cell, the intratumoral mierovessel of hepatic metastases with similar size in both groups were studied with in vivo microscopy (26 and 27 neoplasms in experimental group and control group respectively ) and immunohistochemistry for CD34 (52 and 55 neoplasms in experimental group and control group respectively). Two-tailed student t test was used to determine differences in intratumoral microvessel density (MVD), intratumoral branch density (BD) and CD34 positive intratumoral microvessel density (MVD-CD34) between the small ( < 400 μm in diameter) and large metastases in both groups, and that between thalidomide treated group and control group. Results For the control group, although the MVD and MVD-CD34 of larger metastases was more than that of small metastases respectively [(18.1±3.5)% vs (13.0±3.2) %, t =2.840,P<0.01;(22.9±2.8)vs ( 12. 8±2. 5) vessels per field, t = 9. 860, P < 0. 01 ], the BD was similar to that of small metastases [(110.0±20.5)vs(99.7±17.3) branches/rnm2, t = 1.040,P >0.05]. For the thalidomide treated group, despite the MVD-CD34 of larger metastases was more than that of small metastases [ ( 17.4±2. 3)vs (11.5±2. 5 ) vessels per field, t = 8. 770, P < 0. 01], the MVD and BD was similar to that of small metastases respectively [(14.7±3.5)% vs(13.2±3.3) %, t =0.826,P >0.05; (95.3±18.3)vs (97. 1±21. 0)branches/mm2,t=0. 347,P>0. 05]. The MVD, BD and MVD-CD34 of small metastases were similar to each other between two groups ( t = 0. 098, 0. 392,1. 190; P > 0. 05 ), however, that of large metastases were significantly lower in thalidomide treated group than in control group ( t = 3. 140,2. 870, 9. 850;P < 0. 01 ). Conclusions Thalidomide exerts antiangiogenic effect on the hepatic metastases with angiogenesis only, and the different vascular components in the tumor vasculature demonstrate variousresponses to antiangiogenic therapy.