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整合素连接激酶对裸鼠前列腺癌生长的影响

[Effect of integrin-linked kinase on the growth of prostate cancer in nude mice].

作者信息

Li Qing, Xu Tao, He Pei-ying, Hao Yi-chang, Wang Xiao-feng

机构信息

Department of Urology, Peking University People's Hospital, Beijing 100044, China.

出版信息

Beijing Da Xue Xue Bao Yi Xue Ban. 2010 Aug 18;42(4):374-80.

Abstract

OBJECTIVE

To investigate the effect of the integrin-linked kinase (ILK) small interfering RNA (siRNA) on prostate cancer in nude mice by orthotopic injection of human cell line DU145.

METHODS

The cultured human cell line DU145 was knocked down for ILK using a siRNA .Cellular ILK expression was quantified by RT-PCR and Western blot analysis. Moreover, cell attachment, invasiveness and microfilament dynamics assays were performed. Furthermore, the impact of the ILK siRNA on the prostate cancer was tested using a nude mice model in which prostate cancer was induced by orthotopic injection of human prostate cancer cell line DU145.Gross tumor volume of prostate in nude mice,cell differentiation,the state of apoptosis and proliferation were tested after 5 weeks of injection.

RESULTS

The expression of ILK was suppressed significantly by siRNA, cellular mRNA and protein of ILK decreased 87% and 81% separately. The knockdown of ILK also induced the attachment and invasiveness of DU145 cell growing down. The tumor volume, cell differentiation, apoptosis index and proliferation index of prostate in nude mice of ILK siRNA orthotopic injection model were significantly smaller, better, increased and decreased separately than those in control group.

CONCLUSION

Targeting inhibition of ILK not only decreases attachment and invasiveness of human DU145 cells, but also suppresses the growth and development of prostate cancer of orthotopic injection human DU145 cell line model in nude mice.

摘要

目的

通过原位注射人细胞系DU145,研究整合素连接激酶(ILK)小干扰RNA(siRNA)对裸鼠前列腺癌的影响。

方法

使用siRNA敲低培养的人细胞系DU145中的ILK。通过逆转录聚合酶链反应(RT-PCR)和蛋白质免疫印迹分析对细胞ILK表达进行定量。此外,进行细胞黏附、侵袭和微丝动力学测定。此外,使用原位注射人前列腺癌细胞系DU145诱导前列腺癌的裸鼠模型,测试ILK siRNA对前列腺癌的影响。注射5周后,检测裸鼠前列腺的大体肿瘤体积、细胞分化、凋亡和增殖状态。

结果

siRNA显著抑制ILK的表达,细胞ILK的mRNA和蛋白质分别下降87%和81%。ILK的敲低还诱导了DU145细胞生长的黏附性和侵袭性下降。ILK siRNA原位注射模型裸鼠前列腺的肿瘤体积、细胞分化、凋亡指数和增殖指数分别比对照组显著更小、更好、增加和降低。

结论

靶向抑制ILK不仅降低人DU145细胞的黏附性和侵袭性,还抑制原位注射人DU145细胞系模型裸鼠前列腺癌的生长和发展。

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