Biological activity of 131I labeled angiostatin in vivo and in vitro

Qiuju SHAO; Haifeng XU; Menghui YUAN; Runsuo ZHOU

ABSTRACT

BACKGROUND:

Angiostatin(AS) can effectively inhibit proliferation and migration of vascular endothelial cells and also inhibit tumor angiogenesis.

OBJECTIVE:

To observe the inhibitory action of angiostatin, 131I and 131 I labeled angiostatin(131I-AS) on proliferation of human umbilical vein endothelial cell ECV304 and on mass and volume of Lewis lung carcinoma (LLC) in mice.

DESIGN:

A randomized controlled trial with human umbilical vein endothelial cell ECV304 and Lewis lung carcinoma tumors growing in C57BL/6 mice as subjects of research.

SETTING:

A radiological lab and a nuclear medicine department in a military university.MATERIALS Totally 28 LLC carrying male C57BL/6 mice, weighing(20± 2) g, 5 - 7 weeks old.

METHODS:

131I-AS solutions of four concentrations were made solution A(131I 0. 74 GBq/L, AS 0. 5 mg/L); solution B(131I 0.74 GBq/L, AS 16 mg/L); solution C(131I 1.48 GBq/L, AS 0.5 mg/L); solution D(131I 1.48 GBq/L, AS 16 mg/L). The effect of 131I-AS, AS alone and 131I alone on proliferation of human umbilical vein endothelial cell ECV304 was observed with MTT method. The 28 tumor carrying mice were randomly assigned into 4 groups, in each of which was injected 0.3 mL of 131I AS(131I 11.1 MBq and AS 2.5 mg/kg), AS(2.5 mg/kg), 131I(11.1MBq) and saline respectively for twice with 7 days interval. Then the change in tumor mass and volume was observed.MAIN OUTCOME

MEASURES:

① The inhibition rate on cell proliferation with MTT method; ② Change in tumor mass and volume.

RESULTS:

① The inhibition rate of AS alone(0. 5 -64 mg/L) on ECV304 was (7.3 ± 3.5) % - (41.9 ± 4. 3 )% ( P = 0. 003 vs AS of 0). The inhibition rate of the 4 concentrations of 131I-AS on ECV304 was(23.9±2.8)% ,(58.2±3.9)%, (39. 1 ±4. 1)% and(78.4 ±5.4)%, which were much higher than AS alone or 131I alone( P =0. 000 3) . ② The mean volume of LLC in the four groups were (3 943 ± 236), (5 219 ± 351 ), ( 1 963 ± 126),(7 353 ±350) mm3 respectively. Compared with saline group, the tumor inhibiton rate in the other 3 groups were 46.4% , 29.0% , 73.3% respectively( P =0. 000 1 ).

CONCLUSION:

131I-AS inhibits proliferation of endothelial cells in vitro and inhibits LLC growth in vivo and it outdoes AS or 131I alone.