Endostar, a recombined humanized endostatin, enhances the radioresponse for human nasopharyngeal carcinoma and human lung adenocarcinoma xenografts in mice

Abstract

The purpose of this paper is to determine the efficacy of combining radiation therapy with endostar, a recombined humanized endostatin, in human nasopharyngeal carcinoma and human lung adenocarcinoma xenografts. Tumor xenografts were established in the hind limb of male athymic nude mice (BALB/c-nu) by subcutaneous transplantation. The tumor-bearing mice were assigned into four treatment groups: sham therapy (control), endostar (20 mg/kg, once daily for 10 days), radiation therapy (6 Gray per day to 30 Gray, once a day for 1 week), and endostar plus radiation therapy (combination). The experiment was repeated and mice were killed at days 3, 6, and 10 after initiation therapy, and the tumor tissues and blood samples were collected to analyze the kinetics of antitumor, antiangiogenesis, and antivascularization responses of different therapies. In human nasopharyngeal carcinoma and human lung adenocarcinoma xenografts, endostar significantly enhanced the effects of tumor growth inhibition, endothelial cell and tumor cell apoptosis induction, and improved tumor cell hypoxia of radiation therapy. Histological analyses demonstrated that endostar plus radiation also induced a significant reduction in microvascular density, microvascular area, and vascular endothelial growth factor and matrix metalloproteinase-2 expression compared with radiation and endostar alone respectively. We concluded that endostar significantly sensitized the function of radiation in antitumor and antiangiogenesis in human nasopharyngeal carcinoma and human lung adenocarcinoma xenografts by increasing the apoptosis of the endothelial cell and tumor cell, improving the hypoxia of the tumor cell, and changing the proangiogenic factors. These data provided a rational basis for clinical practice of this multimodality therapy.

Noninvasive monitoring of early antiangiogenic therapy response in human nasopharyngeal carcinoma xenograft model using MRI with RGD-conjugated ultrasmall superparamagnetic iron oxide nanoparticles

“…Endostar, a novel modified recombinant human endostatin, has showed strong antiangiogenic effect on various xenograft tumor model and cancer patients, including NPC. [32][33][34] The results of this study demonstrated that Endostar impeded tumor growth without evident tumor regression and that a significant tumor growth inhibition was not observed until day 8, because Endostar was principally cytostatic rather than cytotoxic. It was also shown that Endostar could reduce the tumor vessels, resulting in the decrease of microvessel density, and subsequently lowered the integrin avβ3 expression.…”

Combination of pigment epithelium‐derived factor with radiotherapy enhances the antitumor effects on nasopharyngeal carcinoma by downregulating vascular endothelial growth factor expression and angiogenesis

“…In addition, some endogenous angiogenic inhibitors have shown an additive effect in combination with irradiation in preclinical studies, such as angiostatin, (43) plasminogen kringle 5 (K5) (44) and endostatin. (45) However, the combined effect of PEDF and irradiation remains unknown. Our data showed that PEDF and irradiation therapy alone modestly inhibited tumor growth compared with the PBS-treated group; however, the PEDF plus radiotherapy group exhibited a significant additive growth inhibitory effect, which is more significant than either treatment alone (P < 0.05, Fig.…”

Effects of VEGF suppression by small hairpin RNA interference combined with radiotherapy on the growth of cervical cancer

“…Shibuya et al (2007) also showed that ZD6474 (an anti-angiogenic drug) could reduce the expression levels of VEGF and epidermal growth factor receptor (EGFR) in tumor tissues, thereby increasing the sensitivity of non-small cell lung cancer for radiotherapy. Recent fundamental research further confirmed that anti-angiogenesis in combined therapy could increase the anti-tumor effect of radiotherapy in human nasopharyngeal cancer and lung adenocancer (Wen et al, 2009).…”