Minimally Invasive Urology Center, Provincial Hospital Affiliated to Shandong University, No. 324 Jingwu Road, Jinan 250001, China.
J Exp Clin Cancer Res. 2013 May 9;32(1):26. doi: 10.1186/1756-9966-32-26.
Our study is to research the effect of inhibited ADAM-17 expression through the Notch pathway in renal carcinoma.
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.
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.
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.
本研究旨在通过 Notch 通路抑制 ADAM-17 的表达来研究其对肾细胞癌的影响。
采用免疫组织化学和 Western blot 检测肾癌细胞组织中 ADAM-17 蛋白的表达。用 CCK-8 检测和 Transwell 检测两种 Notch 通路抑制剂处理 786-o 细胞和 OS-RC-2 细胞后，分别检测细胞增殖和细胞侵袭，用 FCM 检测 786-o 细胞凋亡。
ADAM-17 在 RCC 组织中高表达。与阻断 γ-分泌酶（一种已知的损害 Notch 的机制）相比，阻断 ADAM-17 更有效地下调 Notch1 和 HES-1 蛋白的表达。同样，我们发现，与 γ-分泌酶抑制剂 DAPT 相比，在相同剂量下，ADAM-17 抑制剂 Marimastat 可更有效地降低肾癌细胞的增殖和侵袭能力。当测量 786-o 的凋亡时，得到了类似的结果。
与 γ-分泌酶相比，抑制 ADAM-17 的表达更有效地抑制了 Notch 通路介导的肾癌细胞增殖和侵袭。ADAM-17 可能是未来治疗肾细胞癌的一个新靶点。
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