小鼠sFlt重组腺病毒抑制小鼠Lewis肺癌的生长

Inhibition of mouse Lewis lung cancer via intravenous administration of recombinant mouse sFlt1 adenovirus

背景与目的实体肿瘤组织的生长具有血管依赖性,肿瘤新生血管生成已证实为肿瘤生长的控制点之一。本研究拟探讨编码小鼠可溶性血管内皮生长因子受体1(sFlt1)的复制缺陷型腺病毒对肿瘤新生血管和肿瘤生长的影响。方法应用小鼠Lewis肺癌细胞(LLC)株建立肺癌模型进行抗肿瘤的研究,以编码sFlt1的复制缺陷型重组腺病毒(sFlt1Adv)作为治疗组,编码绿色荧光蛋白的复制缺陷型重组腺病毒(GFPAdv)和生理盐水作为对照组,皮下接种小鼠LLC一周后,经尾静脉给药2次(间隔2周),第二次给药后2周,处死全部实验鼠,剥离肿瘤组织并称重,用3%多聚甲醛固定,用抗CD31作免疫组织化学染色。结果sFlt1Adv治疗组肿瘤明显小于GFPAdv对照组和生理盐水组(P<0.01),其抑瘤率达到71.8%;治疗组的肿瘤微血管密度低于GFPAdv对照组和生理盐水组(P<0.01)。结论复制缺陷型重组腺病毒能抑制肿瘤组织的新生血管形成,从而抑制肿瘤的生长,有较好的应用价值。

Background and objective It has been known that the growth of solid tumors is dependent on angiogenesis, and neoangiogeneses of tumor become main target to control tumor growth. The aims of this study are to investigate the inhibition effect of replicate deficient adenovirus encoding the soluble form of mouse vascular endothelial growth factor receptor 1 （sFlt1 Adv） on angiogenesis and tumor growth in established tumor model. Methods Mouse I.ewis lung cancer cells were inoculated subcutaneously into C57 mice. sFltl Adv, GFP-Adv and normal saline were injected twice intravenously after establishing I.ewis cancer model. Diameters of tumors were measured every other day. Tumors were resected, weighed and fixed in 3% paraformadehyde. Microvessel density of tumors was determined by immunohistochemical staining with anti CD31 antibody. Results The planted tumor volume and weight in sFlt1-Adv group were significantly lower compared with the two controls （P〈0.01）. Its inhibition rate was 71.8%. The microvessel density in sFltl-Advgroup decreased markedly compared with that of the control groups （P〈0. 01）. Conclusion sFlt1 Adv can inhibit the growth of tumor through the inhibition of tumor angiogenesis, sFlt1 Adv may be potentially valuable for clinical treatment of solid tumor.