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神经降压素及其受体1对胶质瘤细胞侵袭的影响

, PP. 2427-2431

Keywords: 胶质瘤,神经降压素,神经降压素受体,侵袭

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Abstract:

目的探讨神经降压素(neurotensin,NTS)及其受体1(neurotensinreceptor1,NTSR1)对恶性胶质瘤细胞迁移和侵袭能力的影响。方法体外实验分为空白对照组,NTS刺激组,NTS+sc-shRNA组和NTS+shNTSR1组,采用慢病毒介导的RNA干扰技术沉默人胶质瘤细胞系U87中NTSR1的表达后采用细胞划痕实验和Transwell侵袭实验检测NTS/NTSR1对胶质瘤细胞迁移和侵袭能力的影响;Westernblot检测NTS/NTSR1对N-钙粘素(N-cadhein)和基质金属蛋白酶-9(MMP-9)蛋白表达水平的影响。在体实验分为实验组shNTSR1-U87和对照组sc-shRNA-U87,建立裸鼠颅内移植瘤模型。利用小动物磁共振技术(MRI)监测裸鼠颅内胶质瘤的生长,评估瘤细胞对瘤周组织的侵袭情况以及NTS/NTSR1对荷瘤鼠生存期的影响。结果NTS/NTSR1促进恶性胶质瘤细胞株U87的体外迁移和侵袭能力,划痕结果显示,NTS刺激组细胞迁移率[(38.02±6.87)%高于空白对照组(13.46±4.49)%,P<0.05]。NTS+shNTSR1组细胞迁移率(9.48±3.08)%低于NTS+sc-shRNA组[(35.48±12.89)%,P<0.05]。Transwell结果也证实,NTS刺激组穿膜细胞光密度值(0.25±0.02)高于空白对照组[(0.16±0.02),P<0.05]。NTS+shNTSR1组光密度值(0.15±0.03)低于NTS+sc-shRNA组光密度值[(0.24±0.04),P<0.05]。NTS/NTSR1上调U87细胞MMP-9的表达并抑制N-钙粘素的表达(P<0.05)。在体实验结果显示,沉默NTSR1抑制荷瘤小鼠颅内胶质瘤的生长和侵袭,延长荷瘤鼠生存期(P<0.05)。结论抑制NTSR1的表达能降低瘤细胞体内外侵袭能力,延长小鼠的生存期。

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