Effects of Gold Nano Particles on HIF-1α and VEGF mRNA Expression and Normalizing Vascellum in Hepatic Tumor of Nude Mice
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摘要: 目的 观察纳米金(goldnano particles,GNP)对裸鼠H22肝癌缺氧诱导因子-1α(hypoxia inducible factor, HIF-1α)、血管内皮细胞生长因子(vascular endothelial growth factor,VEGF)的表达及肿瘤血管 的影响。方法 Balb/c裸鼠14只,肝癌造模后,随机分两组,每组7只实验动物。GNP组:从肿瘤内注入GNP(浓度为500 nmol/L)溶液0.2 ml;对照组:用等量0.9%氯化钠溶液处理,连续用药7d。超声多谱勒分析肿瘤血管形态,测量肿瘤血管直径和血液灌注量;处死裸鼠时测量肿瘤体积,原位杂交检测HIF-1α mRNA及VEGF mRNA表达。结果 (1)GNP组肿瘤体积(0.935±0.129)cm3较对照组(1.573±0.247)cm3下降(P<0.05)。(2)GNP组肿瘤血管直径(0.6397±0.1548)mm及血液灌注量(1.171±0.241)cm3较对照组血管直径(1.1000±0.3247)mm 和血液灌注量(2.357±0.408)cm3减少(P<0.05)。(3)GNP组裸鼠肝癌组织HIF-1α mRNA(15.3±7.4)%、VEGF mRNA(23.7±9.5)%,均较对照组[(67.2±13.1)%,(70.3±14.6)%]明显降低(P<0.05)。结论 GNP可以使裸鼠肝癌血管形态趋于正常,降低肿瘤血液灌注;抑制HIF-1α mRNA、VEGF mRNA表达,抗肿瘤生长。
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关键词:
- 纳米金 /
- 肝细胞癌 /
- 肿瘤血管 /
- 血管内皮细胞生成因子 /
- 缺氧诱导因子-1&alpha
Abstract: Objective To observe the effects of GNP (goldnano particles,GNP) on nude mice hepatic tumor vascular morphology and the expression of hypoxia inducible factor 1α (HIF-1α) and vascular endothelial growth factor (VEGF) mRNA. Methods Hepatocellular cancer cell line H22 were injected subcutaneously into the right armpits of 14 Balb/c nude mice. When the diameter of transplanted tumor reached about 7-8 mm,they were randomly divided into 2 groups, and drugs with GNP or normal saline were injected respectively. For 7 days later, the tumor vascular diameter and blood volume were measured by Doppler ultrasound. When the mice were sacrificed, the tumor's size was calculated and the expression of HIF-1α and VEGF mRNA were detected by in situ hybridization. Results (1)The tumor's size in experiment group (0.935±0.129 cm3) was decreased in comparison with that in control group (1.573±0.247 cm3), there was significantly difference (P<0.05).(2) The tumor's vascular diameter and blood volume in experiment group were (0.6397±0.1548)mm and (1.171±0.241)cm3 respectively, they were all signifi cantly reduced in comparison with those in control group (1.1000±0.3247 mm, 2.357±0.408 cm3)(P<0.05). (3)The expression of HIF-1α mRNA (15.3±7.4%) and VEGF mRNA (23.7±9.5), were dramatically attenuated in comparison with those in control group [(67.2±13.1)%,(70.3±14.6)%] (P<0.05). Conclusion GNP can make nude mice tumor's vascular morphology better and decrease their blood volume, inhibit the expression of HIF-1α mRNA,VEGF mRNA, this situation is benefi t to restrain the tumor growth.-
Key words:
- Nanogold particles /
- Hepatic carcinoma /
- Tumor vascular /
- VEGF /
- HIF-1&alpha
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[1] Rey S,Semenza GL.Hypoxia-inducible factor-1 dependent mechanisms of vascularization and vascular remodelling[J]. Cardiovasc Res,2010,86(2):236-42. [2] Liu WJ,Gu XH,Ding Y,et al.Application of gold nanoparticles in anticancer research[J].Xian Dai Sheng Wu Yi Xue Jin Zhan,2010,10(5):982-5.[刘文佳,谷小虎,丁轶,等.纳米金在抗 肿瘤研究中的应用[J].现代生物医学进展,2010,10(5):982-5.] [3] Fu YW,Pan YL,Qin L,et al. Inhibition of Ang-2 and RGS-5 expression by nanogold results in normalization of vascellum in hepatic tumor [J].Zhongguo Bing Li Sheng Li Za Zhi, 20 11,27(12):2247-50.[傅岳武,潘运龙,覃莉,等.纳米金抑制 Ang-2和RGS-5表达导致裸鼠肝癌血管正常化[J].中国病理生 理杂志,2011,27(12):2247-50.] [4] Pan YL,Zhao XX,Qin L,et al.The sensitization of gold nanoparticles on epirubicin[J].Zhonghua Shi Yan Wai Ke Za Zhi,2011,20(4)??533-5.[潘运龙,赵晓旭,覃莉,等.纳米金对表阿霉 素的增敏作用[J].中华实验外科杂志,2011,20(4):533-5.] [5] Kim SE,Shim KN,Jung SA,et al.The clinicopathological significance of tissue levels of hypoxia-inducible factor-1alpha and vascular endothelial growth factor in gastric cancer[J].Gut Liver,2009,3(2):88-94. [6] Pan YL,Qiu SY,Qin L,et al.Observation of molecular interaction between goldnanoparticle and VEGF165 with atomic forcem icroscope[J].Zhongguo Bing Li Sheng Li Za Zhi,2010,26(12):2 29 5-300.[潘运龙,邱思远,覃莉,等.纳米金与VEGF165分子作 用的原子力显微镜研究[J].中国病理生理杂志,2010,26(12): 22 95-300.] [7] Vaupel P,Mayer A. Hypoxia in cancer: signifi cance and impact on clinical outcome[J].Cancer Metastasis Rev,2007,26(2):225-39. [8] Welen K, Jennbacken K, Tesan T,et al.Pericyte coverage decreases invasion of tumor cells into blood vessels in prostate cancer xenografts[J].Prostate Cancer Prostatic Dis,2009,12(1):41-6.
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