尿激酶受体反义核糖核酸抑制肺癌细胞的侵袭转移

目的用反义核糖核酸(RNA)封闭尿激酶受体的表达,抑制人肺癌细胞株95D的侵袭转移能力,验证反义RNA技术在抗肿瘤中的作用.方法将尿激酶受体(uPAR)反义核糖核酸表达质粒转染具有高度侵袭转移能力的人肺癌细胞株95D,利用改良Bovden小室分析转染细胞的体外侵袭能力,并将转染细胞接种裸小鼠以观察其体内转移能力.结果G418筛选后,鉴定出2个表达uPAR反义RNA细胞克隆,uPAR蛋白质水平相应降低.表达uPAR反义RNA的细胞克隆的体外侵袭能力及在裸小鼠体内的肺转移能力较亲本细胞和空载体对照细胞均有显著性降低(P＜0.05).结论抑制尿激酶受体的表达,能够有效抑制肺癌的侵袭转移,反义RNA技术在抗肿瘤治疗中有良好的应用前景.

Antisense RNA for urokinase receptor inhibits the invasiveness and metastasis of lung carcinoma

Objective To inhibit invasion and metastasis of human lung carcinoma cell line 95D by antisense RNA for urokinase receptor (uPAR). Methods Antisense RNA expression plasmid for uPAR was introduced into the highly metastatic human lung carcinoma cells 95D.Modified Boyden's chamber was used to detect the invasion ability, and nude mice were used to determine metastasis. Results Two transfected clones were found to integrate the antisense expression plasmid into genomic DNA and to express antisense RNA for uPAR. Antisense RNA blocked the uPAR expression in the transfected clones. The evident reductions of the invasiveness of antisense clones were observed by comparison with control cells,95D cells and cells transfected with pcDNA3 vector. The metastatic potential of these two antisense clones decreased significantly in comparison with the contro1s ( P <0.05). Conclusions The results suggest that antisense RNA for uPAR inhibits uPAR expression and leads to a decrease of metastatic potential of 95D cells. Antisense RNA technique may have a valuable application in anti metastatic therapy of human lung carcinoma.