瘦素对人乳腺癌裸鼠移植瘤雌激素受体α、βmRNA的调控作用

目的通过荷人乳腺癌裸鼠模型来进行在体研究外源性人类瘦素对移植瘤组织内雌激素受体(ER)a、β mRNA的调控作用.方法应用人乳腺癌MCF-7细胞制备荷人乳腺癌裸鼠模型,随机分成瘦素实验组(n=30)及0.9%的氯化钠溶液对照组(n=30).实验组采用瘤周皮下注射人重组瘦素连续15 d,对照组给予皮下注射相同剂量0.9%的氯化钠溶液.实时荧光PCR法扩增移植瘤组织内ERα、ERβ mRNA并进行相对定量分析.结果成功建立荷人乳腺癌裸鼠模型,并进行了瘤周皮下注射人类瘦素干预.ERα mRNA表达量在瘦素组高于0.9%的氯化钠溶液组(P＜0.01),ERβmRNA表达量在瘦素组低于0.9%的氯化钠溶液组(P＜0.01).结论通过瘤周皮下注射人类瘦素来干预荷人乳腺癌裸鼠是安全的.ERα与ERβ都可作为人类瘦素的作用靶点.外源性人类瘦素可以上调人乳腺癌裸鼠异种移植瘤内ERαmRNA的表达,下调ERβ mRNA的表达.

Abstract：

Objective To investigate the different effect of exogenous leptin on estrogen receptor α,β mRNA in human breast tumor tissue in nude mice xenograft models. Methods We made nude mice xenograft models of MCF-7 human breast cancer cells cultured in vitro, then divided them into experimental group of]eptin( n = 30)and control group of normal saline( n = 30)randomly. The models of experimental group were injected subcutaneously the recombinant human leptin for 15 consecutive days, the models of control group were injected subcutaneously the same dose of normal saline. A real- time quantitative RT- PCR assay was developed to quantify the expression of estrogen receptor α, β mRNA in tumor tissue, using the relative quantitative analysis. Results The leptin-intervened nude mice xenograft models were safely established. The relative quantitation of estrogen receptor α mRNA was significantly higher in the leptin group than in the normal saline group ( P ＜ 0.01 ), the relative quantitation of estrogen receptor β mRNA was significantly lower in the leptin group than in the normal saline group ( P ＜ 0. 01 ). Conclusion The nude mice xenograft models can be safely intervened with human leptin by subcutaneous injection around tumor.Estrogen receptor is one of the targets of leptin in the progress of breast cancer. Exogenous human leptin can up- regulate the expression of estrogen receptor α and down- regulate the expression of the estrogen receptor βin nude mice xenograft models of human breast tumor.