Experimental study of recombinant human vascular endostatin for breast cancer in nude mice model

Abstract

Objective To explore the effect of recombinant human vascular endostatin(Endostar,YH-16) on MCF-7 human breast cancer cells in nude mice. Methods Forty nude mice were randomized into four groups and received injection with MCF-7 cells. When gross tumor volume reached 1.0 cm3 ,mice were injected subcutaneously once every two days as following for 20 days: (1) O. 9% NS(0. 2 mg/kg) in negative control group;(2) YH-16(20 mg/kg) in YH-16 group; (3) DDP (1 mg/kg) in positive control group; (4) DDP (1 mg/kg) plus YH-16(20 mg/kg) in DDP plus YH-16 group. Mice were killed by cervical spine disloca-tion. And the body weight, tumor volume, rate of tumor inhibited, VEGF, apoptosis rate of tumor cells and pul-monary metastasis rate were detected. Results The means (SD) of tumor volume in DDP plus YH-16 group,positive control group, YH- 16 group and negative control group were 0. 686 (0. 229), 1. 258 (0. 101), 1. 888 (0. 215), 3. 366 (0. 284) cm3, respectively (P <0. 05) ; the rates of tumor inhibited in the four groups were 92. 1% ,57.3 %, 36. 5 % and 0, respectively (P < 0. 05) ; pulmonary metastasis rates were 0, 10%, 20% and 90% ,respectively(P <0. 05) ;the mean (SD) of apoptosis rates of tumor ceils were 31.6% (2. 7%) ,28. 1%(2. 7%), 19. 4% (2. 9%), 15.7% (3.2%), respectively (P < 0. 05). The mean of absorbance of VEGF in the four groups were 0. 530 ± 0. 164,0. 759 ± 0. 210,1. 063 ± 0. 295,1. 268 ±0. 145 (RT-PCR) and O. 260 ±0. 082,0. 348 ±0. 085,0. 461 ±0. 099,0. 556 ± 0. 113(Western blot) ,respectively(P < 0. 05). Conclusion YH-16 can inhibit MCF-7 breast cancer cell growth and distant metastasis in nude mice with little adverse reac-tion. YH-16 has synergistic effect combined with DDP. Key words: Endostatins; Breast neoplasms; Angiogenesis inhibitors; Vascular endothelial growth factors