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雷帕霉素抑制人宫颈癌裸鼠移植瘤生长的作用及其机制

韩 璐, 贺 珊

韩 璐, 贺 珊. 雷帕霉素抑制人宫颈癌裸鼠移植瘤生长的作用及其机制[J]. 肿瘤防治研究, 2013, 40(11): 1036-1040. DOI: 10.3971/j.issn.1000-8578.2013.11.006
引用本文: 韩 璐, 贺 珊. 雷帕霉素抑制人宫颈癌裸鼠移植瘤生长的作用及其机制[J]. 肿瘤防治研究, 2013, 40(11): 1036-1040. DOI: 10.3971/j.issn.1000-8578.2013.11.006
HAN Lu, HE Shan. Rapamycin in Growth Inhibition of Human Cervical Carcinoma HeLa Cell Subcutaneous Xenografts in Nude Mice and Its Mechanism[J]. Cancer Research on Prevention and Treatment, 2013, 40(11): 1036-1040. DOI: 10.3971/j.issn.1000-8578.2013.11.006
Citation: HAN Lu, HE Shan. Rapamycin in Growth Inhibition of Human Cervical Carcinoma HeLa Cell Subcutaneous Xenografts in Nude Mice and Its Mechanism[J]. Cancer Research on Prevention and Treatment, 2013, 40(11): 1036-1040. DOI: 10.3971/j.issn.1000-8578.2013.11.006

雷帕霉素抑制人宫颈癌裸鼠移植瘤生长的作用及其机制

基金项目: 大连市科技局社会发展基金资助项目(2008E13SF195)
详细信息
    作者简介:

    韩璐(1963-),女,博士,主任医师,主要从事妇科肿瘤的研究

  • 中图分类号: R737.33

Rapamycin in Growth Inhibition of Human Cervical Carcinoma HeLa Cell Subcutaneous Xenografts in Nude Mice and Its Mechanism

  • 摘要: 目的 探讨雷帕霉素(rapamycin,RAPA)对人宫颈癌HeLa裸鼠皮下移植瘤生长的抑制作用及其可能的机制。方法 裸鼠皮下接种HeLa细胞,建立人宫颈癌裸鼠皮下移植瘤模型,随机分为对照组、RAPA低剂量组(1.5 mg/kg)、RAPA高剂量组(4.5 mg/kg)。RAPA治疗过程中,检测肿瘤的体积、质量,免疫组织化学法及RT-PCR法检测低氧诱导因子-1α(hypoxia-inducible factor-1alpha, HIF-1α)mRNA、血管内皮生长因子(vascular endothelial growth factor,VEGF)mRNA的表达及肿瘤微血管密度(microvessel density, MVD)。结果 RAPA低剂量组、高剂量组肿瘤生长曲线均减缓;RAPA 低剂量组及高剂量组裸鼠皮下移植瘤平均体积、重量与对照组比较显著减小(P<0.01);低剂量组与高剂量组间比较差异无统计学意义(P>0.05)。RAPA低剂量组及高剂量组VEGF蛋白、VEGF及HIF-1α含量、MVD与对照组比较显著减少(P均<0.01),低剂量与高剂量组间比较,差异无统计学意义(P>0.05)。结论 RAPA对裸鼠皮下移植瘤生长(体积、重量)具有明显的抑制作用,其可能机制是通过抑制HIF-1α的表达抑制VEGF的合成,进而抑制肿瘤组织的血管形成。

     

    Abstract: Objective To evaluate the inhibition effect of rapamycin (RAPA) on the growth of human cervical carcinoma subcutaneous xenografts in nude mice and its possible mechanism. Methods Nude mice were subcutaneously inoculated with HeLa cells to establish a subcutaneous transplantation tumor model of cervical cancer. Mice were randomly divided into 3 groups: control, low(1.5 mg/kg)and high dose (4.5 mg/kg) group. The nude mice were sacrifi ced 2 weeks after drug intervention, and the tumor volume and weight were observed during the therapeutic process. The mRNA and protein expressions of hypoxia-inducible factor-1alpha (HIF-1α), vascular endothelial growth factor (VEGF) and microvessel density(MVD)were detected by immunohistochemistry and RT-PCR. Results The carcinoma cell growth curve was significantly slow down after treated with Rapamycin. Compared with the control group, the average tumor volume and weight,VEGF protein levels,VEGF and HIF-1α mRNA levels, MVD were signifi cantly reduced in the low and high dose groups(P<0.01),with no difference between different dose groups(P>0.05). Conclusion Rapamycin has obviously inhibition effect on Xenograft model in nude mice (volume weight), and the possible mechanism is to inhibit the expression of VEGF through inhibiting HIF-1α, thereby to inhibit the tumor angiogenesis.

     

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出版历程
  • 收稿日期:  2012-09-11
  • 修回日期:  2013-01-30
  • 刊出日期:  2013-11-24

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