Anti-tumor effect of pEgr-1-endostatin-TNF-α recombinant plasmid expression induced by ionizing radiation / 中华放射医学与防护杂志

ABSTRACT

Objective To study the anti-tumor effects of pEgr-1-endostatin-TNF-α generadiotherapy on mice bearing Lewis lung carcinoma, and to explore the mechanism involved. Methods 240 mice with Lewis lung carcinoma were randomly divided into four groups, including control group,irradiation group, liposome group, and liposome combined irradiation group. The plasmids packed by liposome were injected locally into the tumors of the mice, and the tumors of liposome combined irradiation group were irradiated with 10 Gy γ-rays 24 h later. The expression levels of TNF-α and endostatin in mouse serum were measured by ELISA. Then the tumor growth rates at different time were observed. Tumor angiogenesis density were estimated on frozen sections stained with CD31 by using the Chalkley counting method to vessel hot-spots. The tumor inhibition rates were also calculated. Results Radiation induced the expression of pEgr-1-endostatin-TNFα. The endostatin and TNF-α were expressed steadily for about 4 weeks. The highest levels of expression of the endostatin and TNF-α were (52. 64 ±4. 19)and( 12. 01 ±0. 87 ) ng/ml at 2 week. The expression levels of TNF-α and endostatin were higher in combined therapy group than those in other groups( F = 29. 726,P ＜ 0.05 ). Compared with the control group, the density of tumor angiogenesis were depressed [ (4.7 ± 0. 8 ) vs ( 10.0 ± 1. 2)/field, t = 14. 063, P ＜ 0.05 ] and tumor growth were significantly inhibited compared to the control group and irradiation group [ (5907. 2 ±78.6), (4653.4±32.8) and (763.5 ± 12.3) mm3, F= 16.415,P ＜0.05)]. Conclusions The expression of pEgr-1-endostatin-TNFα could be induced by irradiation in dose- and time-dependent manner. The effect of antitumor and angiogenesis inhibition may be more significant than irradition.