[关键词]
[摘要]
目的:研究IL27对肿瘤血管生成的抑制作用及其机制。方法: IL27基因稳定转染的人食管癌细胞(Eca109/IL27)接种于裸鼠,建立荷瘤裸鼠模型,观察肿瘤生长情况和裸鼠生存期。用ELISA法检测脾细胞IFNγ的分泌水平;免疫组化法检测瘤组织中VEGF和CD34的表达,并通过CD34的水平计算微血管密度;用RTPCR法检测肿瘤组织趋化因子IP10、MIG mRNA的表达水平。结果:接种Eca109/IL27细胞荷瘤小鼠的生存期较接种野生型Eca109细胞(未转染质粒)和Eca109/LXSN细胞(空载体质粒转染)小鼠的生存期明显延长(P<0.05)。接种Eca109/IL27细胞的裸鼠瘤组织中VEGF和CD34的表达水平显著性低于接种Eca109细胞和Eca109/LXSN细胞,微血管密度显著降低(均P<0.01)。Eca109/IL27组小鼠脾细胞产生较高水平的IFNγ(P<0.05),趋化因子IP10和MIG mRNA的表达水平也显著性高于接种Eca109细胞组和Eca109/LXSN细胞组(P<0.05)。结论: IL27在裸鼠体内通过上调IP10和MIG表达抑制肿瘤血管生成,从而发挥抗肿瘤作用。
[Key word]
[Abstract]
Objective: To study the inhibitory effect of IL27 against human tumor angiogenesis and the related mechanisms. Methods: Human esophageal carcinoma cells (Eca109/IL27) stably transfected with IL27 gene were injected into nude mice to establish tumorbearing mouse model. The survival time and tumor growth were observed. IFNγ level secreted by splenocytes was measured by ELISA. Expression of VEGF and CD34 was detected by immunohistochemistry method and MVD was calculated according to CD34 level. RTPCR was used to detect the expression of IP10 and MIG mRNA in the tumor tissues. Results: The survival time of mice injected with Eca109/IL27 cells was significantly longer than those of mice injected with wide type Eca109 or Eca109/LXSN (blank vector) cells (P<0.05). Expression of VEGF and CD34 in Eca109/IL27inoculated mice was lower than those in Eca109 or Eca109/LXSN groups. Production of IFNγ by splenocytes in mice injected with Eca109/IL27 cells was higher than those with Eca109 and Eca109/LXSN (P<0.05). MIG and IP10 mRNA expression was also higher than those in Eca109 or Eca109/LXSN injected mice (P<005). Conclusion: IL27 can inhibit tumor angiogenesis in nude mice through upregulating the expression of MIG and IP10, and thus exerts antitumor effect
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[基金项目]
科技部重大科技攻关课题 (No. 2006BAI02A07)