Diversin在人脑星形细胞瘤组织中的表达及其对肿瘤细胞增殖和侵袭的影响

Expression of Diversin in human astrocytomas and its relationships with proliferation and invasion of tumor cells

目的观察人脑星形细胞瘤组织中Diversin表达及其对肿瘤细胞增殖和侵袭的影响,并探讨其作用机制。方法采用免疫组化法检测105例人脑星形细胞瘤组织中的Diversin。通过siRNA沉默技术调控星形细胞瘤U87细胞中Diversin的表达,并以MTT、Transwell、Western blot、实时荧光定量PCR等方法检测肿瘤细胞的增殖和迁移能力及细胞Diversin、p-JNK、MMP-9的表达。结果 Diversin在星形细胞瘤的组织学分级Ⅰ、Ⅱ、Ⅲ级中的表达阳性率分别为0、19.2%、48.9%,P均<0.01。对照组与干扰组U87细胞增殖指数分别为2.01±0.42、1.62±0.14,P<0.05;穿膜细胞数分别为(57±6)、(39±6)个,P<0.05;Diversin、p-JNK、MMP9 mRNA及蛋白表达均下降,P均<0.05。结论 Diversin可随星形细胞瘤组织学分级而升高,可作为判断其生物学行为的标记物;Diversin能够通过JNK途径促进人脑星形细胞瘤的增殖与侵袭,并可能成为治疗该肿瘤的新靶点。

Objective To observe the expression of Diversin in human astrocytomas and its relationships with proliferation and invasion of tumor cells,and to investigate its mechanism. Methods The expression of Diversin was detected by immunohistochemical method in 105 cases of astrocytoma tissues. Small interfering RNA( siRNA) knockdown was performed in U87 cell line to regulate the Diversin expression. MTT,Transwell,Western blotting and real-time fluorescent quantitative PCR were used to detect the cell proliferation and migration ability as well as the expression of Diversin p-JNK and MMP-9. Results The positive expression rates of Diversin in the histological gradeⅠ,Ⅱand Ⅲ of astrocytoma were19. 2% and 48. 9%( all P < 0. 01). The proliferation indexes of U87 cells in the control and interference groups were 2. 01± 0. 42 and 1. 62 ± 0. 14( P < 0. 05),and the cells moved through the membrane were( 57 ± 6) and( 39 ± 6)( P <0. 05). The protein and mRNA expression of Diversin p-JNK and MMP9 was significantly decreased( all P < 0. 05). Conclusions Diversin increases with the increased histological grades of astrocytoma and it may be used as the biological behavior marker of astrocytomas. Meanwhile,Diversin can promote the proliferation and invasion of astrocytomas by the way of JNK,and thus it can be a new target for treatment of the tumor.