Sensitization effect of endostatin for 125I brachytherapy on transplanted tumor in nude mice

Objective To investigate the radiation sensitization effect of endostatin on transplanted tumors in nude mice with 125I radioactive seed. Methods Mice were randomly assigned to four groups (n=20) : control group (group A) , 125I radioactive seed group (group B) , endostatin group (group C) , and 125I radioactive seed combined with endostatin group (group D) . When the diameter of the transplanted tumor was greater than 2 cm, 125I radioactive particles were implanted. The prescription dose was 20 Gy. Treatment planning system was used to calculate the target area and size of tumors. Endostatin was injected intraperitoneally at 20 mg/kg once every day for 14 days, and the changes in tumor growth and size were observed. The animals were sacrificed at 15 and 30 days. The expression levels of vascular endothelial growth factor (VEGF) and microvessel density (MVD) in tumor tissues were detected by immunohistochemistry, whereas αvβ3 mRNA levels were determined by RT-PCR. Results Compared with groups B and C, the tumor size, tumor weight, and tumor growth inhibitory rate of group D significantly increased at 15 and 30 days. The tumor size, tumor weight, and tumor growth inhibitory rate of groups B and D significantly increased at 30 days compared with those at 15 days. Immunohistochemical staining revealed that the expression levels of VEGF and MVD in group D were significantly different at 15 and 30 days compared with those in groups A, B, and C. The expression of VEGF and MVD in group C was significantly different at 15 and 30 days compared with that in groups A and B. VEGF and MVD in group C were significantly up-regulated at 30 days compared with those at 15 days. RT-PCR analysis demonstrated that the expression of αvβ3 mRNA in group B obviously increased with time compared with that in group A. Compared with group A, αvβ3 mRNA in group B was up-regulated, whereas αvβ3 mRNA in groups C and D was significantly down-regulated. Compared with groups C and B, group D exhibited a statistically significant difference. Conclusion Endostatin is helpful to brachytherapy of lung tumor with radiosensitizing enhancement effects. Changes in VEGF, MVD, and αvβ3 mRNA may be the rational treatment mechanism. Key words: Endostatins; Lung neoplasms; Radiation-sensitizing agents; Brachytherapy