目的：筛选靶向Survivin基因的抗肿瘤siRNA前体药物，并且探讨其抑制肿瘤细胞侵袭和迁移的分子机制。方法：采用MTT法检测Survivin siRNA脂质体对非小细胞肺癌细胞株H1299、肝癌细胞株SMMC-7721、甲状腺癌细胞株8505C、乳腺癌细胞株MCF-7、结肠腺癌细胞株HCT-116和食管癌细胞株EC109增殖的抑制作用，选择对Survivin-siRNA最敏感的8505C细胞株进行后续研究；分别采用划痕法和Transwell法测定Survivin-siRNA对8505C细胞株迁移和侵袭的影响，采用RT-PCR法和Western blotting测定Survivin-siRNA对8505C细胞株Survivin、基质金属蛋白酶-9（MMP-9）和粘着斑激酶（FAK）mRNA和蛋白水平表达的影响。结果：（1）Survivin-siRNA对H1299、SMMC-7721、8505C、MCF-7、HCT-116和EC109细胞株均有一定程度的抑制作用，其中对8505C细胞株抑制作用最强（IC₅₀=5.83 μg·ml^-1）；（2）癌细胞迁移实验中，Survivin-siRNA可剂量依赖性增大划痕刻度（P<0.05）；（3）癌细胞侵袭实验中，Survivin-siRNA可剂量依赖性减少穿膜细胞数量；（4）在RT-PCR实验中，Survivin-siRNA可剂量依赖性降低8505C细胞株中Survivin、MMP-9和FAK mRNA表达；（5）在Western blotting实验中，Survivin-siRNA可剂量依赖性降低8505C细胞株中Survivin、MMP-9和FAK蛋白表达。结论：Survivin-siRNA作为新型的抗肿瘤药物对甲状腺癌8505C细胞增殖具有较强的抑制作用，并且可以抑制8505C细胞的迁移和侵袭，这可能与其抑制细胞Survivin、MMP-9和FAK的表达有关。

[1] PEROUKIDES S,BRAVOU V,ALEXOPOULOS A,et al.Survivin overexpression in HCC and liver cirrhosis differentially correlates with p-STAT3 and E-cadherin[J].Histol Histopathol,2010,25(3):299-307.
[2] PLEWKA D,JAKUBIEC-BARTNIK B,MOREK M,et al.Survivin in ovary tumors[J].Ginekol Pol,2015,86(7):525-530.
[3] JAISWAL P K,GOEL A,MITTAL R D.Survivin:A molecular biomarker in cancer[J].Indian J Med Res,2015,141(4):389-397.
[4] LU Y H,LUO X G,TAO X.Survivin gene RNA interference induces apoptosis in human HL60 leukemia cell lines[J].Cancer Biother Radiopharm,2007,22(6):819-825.
[5] LIU F,LIU S,HE S,et al.Survivin transcription is associated with P-glycoprotein/MDR1 overexpression in the multidrug resistance of MCF-7 breast cancer cells[J].Oncol Rep,2010,23(5):1469-1475.
[6] LI J Y,GU X,YIN H Z,et al.Protective effect of ischemic preconditioning on hepatic ischemia-reperfusion injury by advancing the expressive phase of survivin in rats[J].Hepatobiliary Pancreat Dis Int,2009,7(6):615-620.
[7] NAMBA H,YAMASHITA S.Gene abnormalities in thyroid cancer[J].Nippon Rinsho,2007,65(11):1967-1972.
[8] 牛志云,成志勇,刘英杰,等.整合素α5β1介导的粘着斑激酶和细胞外信号调节激酶信号传导通路对K562细胞增殖的影响[J].中山大学学报(医学科学版),2009,30(6):728-732.
[9] HSIA D A,MITRA S K,HAUCK C R,et al.Differential regulation of cell motility and invasion by FAK[J].J Cell Bio1,2003,160(5):753-767.
[10] 徐晓艳,裴陆田,李秀霞.非小细胞肺癌中MMP-9和MMP-13的表达及意义[J].临床与实验病理学杂志,2014,30(12):1358-1364.
[11] QIAO Z K,LI Y L,LU H T,et al.Expression of tissue levels of matrix metalloproteinases and tissue inhibitors of metalloproteinases in renal cell carcinoma[J].World J Surg Oncol,2011,103(3):243-247.
[12] 韦花媚,刘坤平,罗春英,等.MMP-9及HIF-1α在鼻NK/T细胞淋巴瘤表达中的作用研究[J].中国免疫学杂志,2016,32(6):863-865.
[13] HERSZÉNYI L,HRITZ I,LAKATOS G,et al.The behavior of matrix metalloproteinases and their inhibitors in colorectal cancer[J].Int J Mol Sci,2012,13(10):13240-13263.