摘要
目的探讨血管内皮生长因子(VEGF)反义寡核苷酸(antisenseoligode-oxyribonucleotide,ASODN)在人甲状腺髓样癌(MTC)裸鼠模型中的抑瘤作用。方法构建12只MTC裸鼠模型,随机分为三组。治疗结束后1周,杀死全部瘤鼠,切取瘤体,测算瘤质量和IR以评价肿瘤生长情况,瘤组织石腊切片分别行HE、免疫组化(IHC)和DNA末端原位标记法(TUNEL法)染色以评价组织病理构造、VEGF与Survivin蛋白表达和细胞凋亡的变化。结果HE染色显示ASODN组具有明显减低的血管新生特点。此外,相对于正常组和SODN组,ASODN组具有显著的VEGF[(0.12±0.02)、(0.15±0.02)、(0.08±0.02)]和Sur-vivin[(0.17±0.03),(0.18±0.02),(0.09±0.02)]低表达、低瘤质量[(0.53±0.02)g,(0.54±0.03)g,(0.45±0.02)g]、高抑瘤率[(0±3.44)%,(-2.36±4.72)%、(15.57±3.22)%]和高凋亡[(4.91±0.67)%,(4.46±1.01)%,(24.68±1.22)%]特点(各P<0.01),而正常组与SODN组间未见上述各特点的统计学差异(各P>0.05)。结论针对人MTCVEGF基因沉默治疗能够达到明显抑瘤效果,此效果至少部分通过抑制肿瘤血管新生和促进肿瘤调亡而实现。这提示VEGF基因在人MTC中具有重要意义,可能成为人MTC基因靶向沉默治疗的重要候选基因之一。
OBJECTIVE： To evaluate the inhibitory effects of VEGF antisense oligodeoxyribonucleotide （ASODN） on human medullary thyroid cancer （MTC） inoculated into nude mouse. METHODS： Twelve nude mouse, models bearing human MTC were constructed and randomly divided into three groups. All nude mice were sacrificed one week after treament; tumors were fully resected from each mouse and measured for tumor weight and inhibitory rate （IR） of tumor growth; paraffin sections of each tumor were made, and respectively stained with HE, immunohistochemical or Tdt-mediated dUTP nick end labeling （TUNEL） method to evaluate the variation of histopathological construction, survivin and VEGF protein expression, and apoptosis. RESULTS： HE staining results showed obviously depressed angiogenic characteristics in ASODN group. Compared with nor mal or SODN group, ASODN group possessed significant traits of lower expression of VEGF [ （0.12 ± 0.02 ）, （ 0.15 ± 0.02 ）, （ 0.08 ±0.02）] and survivin [（0.17±0.03）, （0. 18±0.02）, （0.09± 0.02）] protein, lower tumor weight [（0.53 ±0.02） g, （0.54 ± 0.03） g,（0.45±0.02） g], higher IR [（0±3.44）%, （-2.36± 4.72）%, （15.57±3.22）%], and higher apoptosis [（4.91± 0.67）%,（4.46±1.01）%,（24.68±1.22）%] （each P〈0.01）, but no significance was found between normal group and SODN group for these traits （each P〉0.05 ）. CONCLUSION： VEGF targeting genetic silence therapy could achieve significantly inhibitory effect on tumor growth in human MTC, at least in part by inhibiting tumor angiogenesis and promoting tumor apoptosis. This indicates that VEGF gene plays an important role in human MTC, and may be considered as one of important backup genes for gene targeting silence therapy of human MTC.
出处
《中华肿瘤防治杂志》
CAS
2006年第19期1452-1456,共5页
Chinese Journal of Cancer Prevention and Treatment
