摘要
目的探讨Tie-2小干扰RNA(siRNA)对HepG2细胞裸鼠皮下移植瘤的作用。方法将HepG2肿瘤细胞植于6周龄鼠后背皮下,荷瘤鼠分为对照组及实验组,分别用生理盐水/脂质体及Tie-2-siRNA/脂质体瘤内注射,检测基因治疗前后肿瘤体积、质量变化,血清AFP、MVD及肿瘤组织学变化。结果治疗组治疗后第4、7及10d,抑瘤率分别为26.94%、53.01%及68.91%;肿瘤体积分别为118.47、111.57及104.59mm3,明显小于对照组的162.17、237.46及336.41mm3,差异有统计学意义(P<0.01)。肿瘤瘤重治疗组轻于对照组〔(0.89±0.09)gvs(1.24±0.03)g,P<0.01〕;AFP值治疗组明显小于对照组〔(107.66±24.13)ng/mlvs(266.08±50.96)ng/ml,P<0.01〕;MVD值治疗组亦明显小于对照组(34.63±4.07vs81.01±9.44,P<0.01)。病理组织学显示,对照组肿瘤体积大,异形明显;治疗组可见肿瘤以坏死为主要病理改变,有大片坏死灶。治疗组只有2例在坏死灶与未坏死灶肿瘤间可见凋亡细胞。结论Tie-2-siRNA可抑制肿瘤生长和肿瘤血管生成,为肝癌的基因治疗开辟了新的思路。
Objective To explore the effect of Tie-2 small interference RNA （siRNA） treatment in human hepatoma transplanted subcutaneously in nude mice. Methods Tumor cells were implanted in the hind flank of male nude mice of 6 weeks. Tumor-bearing mice were divided into two groups （gene therapy group and control group） and injected intra-tumorally with Tie-2-siRNA/Lipofectamine and saline/Lipofectamine respectively. The tumor volume and weight, serum AFP and microvessel density （MVD） and the histological change of the tumor were tested after gene therapy. Results The growth inhibitory rates in gene therapy group were 26.94 %, 53.01% and 68.91% on day 4, 7 and 10 after gene therapy respectively. The tumor volumes of gene therapy group （118.47, 111.57 and 104.59 mm3） were smaller than those of the control group （162. 17, 237.46 and 336.41 mm^3） respectively （P〈0.01）, and the weight of tumor in gene therapy group was lighter than that of the control group[0.89±0.09） g vs （1.24±0.03）, P〈0.01]. The AFP value in gene therapy group was obviously lower than that of the control group [（107.66±24.13） ng/ml vs （266.08±50.96） ng/ml, P〈0.01]. There was significant diference of MVD between the gene therapy group （34.63±4.07） and the control group （81.01±9.44） with the method of immunohistochemitry （P〈0.01）. Histopathology in the control group showed that the tumor volumes were bigger, and a high atypic of tumor cells were seen. The main pathological changes in tumor tissue of gene therapy group were necrosis, there were massive necrosis. The apoptosis cells were seen in the both of necrosis and non-necrosis areas in only 2 mice of gene therapy group. Conclusion Tie-2-siRNA inhibits the tumor growth and tumor angiogenesis, and is a possible new approach for liver neoplasm gene therapy.
出处
《中国普外基础与临床杂志》
CAS
2007年第5期543-546,共4页
Chinese Journal of Bases and Clinics In General Surgery
