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目的探讨存活素(Survivin,SVV)、血管内皮生长因子(VEGF)反义寡核苷酸(ASODN)联合治疗裸鼠骨肉瘤。方法构建荷骨肉瘤裸鼠模型,采用瘤内注射给药方式(5 mg/kg体重),以反义SVV、反义VEGF对瘤鼠进行联合干预治疗1周,并与各单药组和空白对照组进行比较,观测各组裸鼠肿瘤生长情况、评估瘤体病理形态,免疫组织化学法检测移植瘤组织SVV、VEGF蛋白表达,DNA末端原位标记法(TUNEL法)检测肿瘤细胞凋亡水平。结果与对照组比较,各治疗组肿瘤生长均不同程度受抑,以联合组最为显著,瘤重仅为(0.52±0.01)g,抑瘤率IR为(42.80±0.88)%;各治疗组肿瘤细胞中SVV、VEGF蛋白表达有所减低,肿瘤细胞出现凋亡坏死改变,其中联合组细胞凋亡指数AI[(27.90±3.66)%]显著高于对照组[(7.10±2.05)%,X~2= 46.27,P<0.01]。结论联合应用SVV与VEGF ASODN将对裸鼠荷骨肉瘤发挥更强的抗瘤效应。
Objective To investigate the combined treatment of survivin (SVV) and vascular endothelial growth factor (VEGF) antisense oligonucleotide (ASODN) in osteosarcoma of nude mice. Methods The osteosarcoma nude mice model was established by intratumoral injection (5 mg / kg body weight). Antisense SVV and antisense VEGF were used to treat the mice for one week. The control group were compared to observe the tumor growth of nude mice in each group, to assess the pathological morphology of tumor, to detect the expression of SVV and VEGF protein in tumor tissue by immunohistochemistry, and to detect the apoptosis level of tumor cells by TUNEL method . Results Compared with the control group, the growth of tumor in each treatment group was inhibited to varying degrees, the most significant was in combination group, the tumor weight was only (0.52 ± 0.01) g, and the tumor inhibition rate (IR) was (42.80 ± 0.88)%; The expression of SVV and VEGF in the cells decreased and the apoptosis and necrosis of the tumor cells changed. The apoptosis index AI in the combined group was significantly higher than that in the control group [(27.90 ± 3.66)% [(7.10 ± 2.05)%, X ~ 2 = 46.27, P <0.01]. Conclusion Combined application of SVV and VEGF ASODN will exert stronger anti-tumor effect on osteosarcoma in nude mice.