Endostar, a recombined humanized endostatin, enhances the radioresponse for human nasopharyngeal carcinoma and human lung adenocarcinoma xenografts in mice.
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.
Wen
Qing-Lian
QL
State Key Laboratory Biotherapy, Cancer Center, West China Hospital, West China School of Medicine, Sichuan University, Chengdu, China.
Meng
Mao-Bin
MB
Yang
Bo
B
Tu
Ling-Li
LL
Jia
Li
L
Zhou
Lin
L
Xu
Yong
Y
Lu
You
Y
D000230:Adenocarcinoma / Q000532:radiotherapy / Q000628:therapy; D000818:Animals; D002277:Carcinoma / Q000532:radiotherapy / Q000628:therapy; D003131:Combined Modality Therapy; D043169:Endostatins / Q000235:genetics / Q000627:therapeutic use*; D006801:Humans; D007279:Injections, Subcutaneous; D008175:Lung Neoplasms / Q000532:radiotherapy* / Q000628:therapy*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009303:Nasopharyngeal Neoplasms / Q000532:radiotherapy* / Q000628:therapy*; D009368:Neoplasm Transplantation; D011994:Recombinant Proteins / Q000627:therapeutic use; D023041:Xenograft Model Antitumor Assays
D043169:Endostatins; D011994:Recombinant Proteins; C522911:endostar protein