Antitumor activity of Endostar combined with radiation against human nasopharyngeal carcinoma in mouse xenograft models

Abstract

Radiation treatment for nasopharyngeal carcinoma (NPC) is common and effective. However, local recurrence occurs frequently. Endostar, a novel recombinant human endostatin, is an antiangiogenic drug with a potent antitumor effect. The present study aimed to observe and explore the radiosensitization effects of Endostar on NPC and its underlying mechanism. The NPC subcutaneous transplantation tumor animal model was established to evaluate the antitumor activity of Endostar combined with radiation (Endostar + radiation) treatment compared with monotherapy (Endostar or radiation). Tumor growth and tumor weight were measured to evaluate the antitumor effect. The level of vascular endothelial growth factor (VEGF) and microvessel density (MVD) were measured using immunohistochemical staining of the tumor tissues. Significant antitumor activity was found in the Endostar + radiation group. The tumor inhibition rates of Endostar, radiation and Endostar + radiation were 27.12, 60.45 and 86.11%, respectively. The VEGF levels in the tumor tissue in the Endostar + radiation group were lower than those in the radiation and control groups. The MVD in the tumor tissues in the Endostar + radiation group was 12.2±2.5, lower than that in the Endostar (29.3±3.4), radiation (23.5±3.6) and control (44.7±5.1) groups. These results suggest that Endostar increases the radiation sensitivity of NPC-transplanted tumors in nude mice by lowering VEGF expression. In this study, the NPC animal model was established, which reflects the efficacy of clinical combination therapies and the combination of Endostar and radiation. The mechanisms of the combination therapies should be further investigated using this model.

Figure 1

Therapeutic effects of the different treatments on NPC tumors in mice. Mice with NPC tumors were divided into four groups (n=6). Groups A, B, C and D were treated with normal saline, Endostar, radiation and Endostar + radiation, respectively. The tumor growth inhibition in group A was 0; this was not included in the graph. ^*P<0.05 and ^**P<0.01 vs. group D, ^#P<0.05 vs. group C. NPC, nasopharyngeal carcinoma.

Figure 2

Hotspots of CD34 immunohistochemical staining and MVD in NPC tumor tissues. Tissues were treated with (A) normal saline; (B) Endostar; (C) radiation and (D) Endostar + radiation (×400). The histological sections stained for CD34 and developed with the DAB chromogen were examined to identify 5 separate zones (hotspots) containing high numbers of discrete CD34 staining sites (dyed claybank). The MVD of NPC tumor tissues in group A, B and C were significantly different from group D (^**P<0.01 and ^*P<0.05 vs. group D). MVD, microvessel density; NPC, nasopharyngeal carcinoma.

Figure 3

Immunohistochemical staining images of VEGF in tumor sections. Tissues were treated with (A) normal saline; (B) Endostar; (C) radiation and (D) Endostar + radiation (n=6) (×200). The VEGF expression in groups A, B, C and D were evaluated as positive, weakly positive, strongly positive and weakly positive, respectively. Semi-quantitative VEGF expression levels in groups A and C were significantly different from group D (P<0.05). VEGF, vascular endothelial growth factor.