Inhibition of ADAM-17 more effectively down-regulates the Notch pathway than that of γ-secretase in renal carcinoma

Journal of Experimental & Clinical Cancer Research

Haiyan Jia¹  Xunbo Jin²  Zhen Guo² 

[1] Shandong traffical hospital, No.11 Wuyingshan Road, Jinan, 250000, China;Minimally Invasive Urology Center, Provincial Hospital Affiliated to Shandong University, No. 324 Jingwu Road, Jinan 250001, China

关键词: γ-secretase;    Marimastat;    Apoptosis;    Renal cell cancer;    Notch;    ADAM-17;   

Others  :  825140
DOI  :  10.1186/1756-9966-32-26

 received in 2013-03-28, accepted in 2013-05-02,  发布年份 2013

【 摘 要 】

Background

Our study is to research the effect of inhibited ADAM-17 expression through the Notch pathway in renal carcinoma.

Methods

Immunohistochemistry and western blot were used to examine the expression of ADAM-17 protein in renal cancer tissues. Proliferation and cell invasion of 786-o cells, as well as OS-RC-2 cells, after treatment with two different inhibitors of the Notch pathway, were examined by CCK-8 assay and Transwell assay, respectively. 786-o cell apoptosis was measured using the FCM test.

Results

ADAM-17 was highly expressed in RCC tissues. Compared with blocking γ-secretase, a known mechanism of impairing Notch, blockade of ADAM-17 more effectively down-regulated the expressions of Notch1 and HES-1 proteins. Similarly, we found that the ADAM-17 inhibitor, Marimastat, could more efficiently reduce renal cell proliferation and invasive capacity in comparison with the γ-secretase inhibitor DAPT when used at the same dose. Similar results were obtained when apoptosis of 786-o was measured.

Conclusion

Compared with γ-secretase, inhibition of ADAM-17 expression more effectively inhibits Notch pathway-mediated renal cancer cell proliferation and invasion. ADAM-17 may be a new target for future treatment of renal carcinoma.

【 授权许可】

   
2013 Guo et al.; licensee BioMed Central Ltd.

【 图 表 】

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