维甲酸对肾母细胞瘤分化诱导和生长抑制的实验研究

Experimental study of differentiation and growth suppression of Wilms' tumor in response to All-trans-retinoic acid

目的 研究维甲酸对肾母细胞瘤是否具诱导分化和体内生长抑制作用。方法 建立人类肾母细胞瘤裸小鼠肾原位移植的模型;荷瘤裸小鼠30只均分两组,分别口服维甲酸30mg·kg^(-8)·d^(-1)和等量芝麻油;测量治疗和对照组裸小鼠体重和移植瘤重量,光镜、电镜观察两组移植瘤的形态学改变,流式细胞仪分析增殖指数,RT-PCR半定量检测IGF2和H19mRNA含量。结果 两组裸小鼠体重差异无显著性意义(P>0.05);维甲酸治疗组裸小鼠移植瘤重量增长显著低于对照组(P<0.05),增殖指数PI也低于对照组(P<0.05)。光镜下移植瘤组织学类型为胚基-上皮混合型,电镜下显示治疗组移植瘤分化较对照组好,出现一些发育成熟的结构如微绒毛、基底膜等;两组移植瘤都扩增出IGF2mRNA治疗组IGF2mRNA灰度值0.950±0.146,低于对照组的1.071±0.238,但统计学比较差异无显著意义。H19在两组裸小鼠移植瘤瘤中都没有检测出阳性转录产物。结论 维甲酸通过诱导肾母细胞瘤分化发挥抑瘤作用,这一效应与IGF2和H19表达调控没有直接联系。

Objective To study All-trans-retinoic acid induced differentiation and growth suppres- sion of Wilms' tumor in vivo. Methods An orthotopic xenografts model of human Wilms' tumor was de- veloped in nude mice. Randomly, a total of 30 nude mice bearing orthotopic xenografts of human Wilms' tumor were equally divided into experimental and control groups. The experimental group was administered with 30 mg/kg·d retinoic acid dissolved in 0.1 ml sesame oil starting 3 weeks after tumor transplantation, and the control group received equivalent volume of sesame oil. The weight of transplanted tumors and their host nude mice were directly measured. Proliferation index (PI) was evaluated in transplanted tumor by FCM. Also, transplanted tumor was subjected to light microscopic observation on morphological differ- entiation and RT-PCR amplification for insulin - like growth factor 2 (IGF2) and H19 mRNA. Results No significant difference was detected in body weight of mice between the experimental and control (P> 0.05). The transplanted tumors derived from nude mice of experimental group increased in weight less than those from control (P<0.05). PI of the experimental group (17.8 ± 2.8) was also lower than that from control (20.8 ± 2.1, P<0.05). Moreover, better morphological differentiation appearing could be noted in experimental group under electronic microscope. IGF2 mRNA was amplified in transplanted tumor but no significant difference was found in semiquantitative value of RT-PCR products between the two groups. H19 transcripts were negative amplification in all tumor samples. Conclusion Retinoic acid plays a role in inhibition Wilms' tumors from growth as xenografts in nude mice by inducing differentiation, which has no direct linkage with regulation of IGF2 and H19 transcription.