Silencing ADAM10 inhibits the in vitro and in vivo growth of hepatocellular carcinoma cancer cells
Silencing ADAM10 inhibits the in vitro and in vivo growth of hepatocellular carcinoma cancer cells
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DOI：
10.3892/mmr.2014.2652
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发表时间：
2015-01-01
影响因子：
3.4
通讯作者：
Wang, Guangyi
中科院分区：
文献类型：
--
作者：
Liu, Songyang;Zhang, Wei;Wang, Guangyi
解整合素和金属蛋白酶 10 (ADAM10) 是一种与多种癌症转移相关的跨膜蛋白。然而，人们对 ADAM10 在肝细胞癌 (HCC) 中的作用知之甚少。本研究的目的是评估 ADAM10 的下调是否影响 HCC 细胞增殖、细胞周期、细胞迁移和细胞侵袭。构建携带ADAM10的重组小发夹RNA表达载体，然后转染入HepG2人HCC细胞系。通过 RNA 干扰下调 ADAM10 后，测定体外细胞增殖、细胞周期、细胞迁移和细胞侵袭以及体内肿瘤生长。结果表明，使用RNA沉默方法下调HepG2肿瘤细胞中ADAM10的表达可显着抑制体外细胞增殖、细胞迁移和细胞侵袭以及体内肿瘤生长。此外，ADAM10 沉默能够显着减少磷酸肌醇 3-激酶 (PI3K) 和 Akt 的组成型磷酸化，这意味着 ADAM10 至少部分参与 PI3K/Akt 信号通路的激活。这些结果表明ADAM10在调节HCC的增殖和转移中具有重要作用。因此，ADAM10 是预防 HCC 肿瘤转移的有前景的治疗靶点。
A disintegrin and metalloprotease 10 (ADAM10) is a transmembrane protein associated with metastasis in a number of types of cancer. Little is known, however, regarding the role of ADAM10 in hepatocellular carcinoma (HCC). The aim of the present study was to evaluate whether downregulation of ADAM10 effects HCC cell proliferation, cell cycle, cell migration and cell invasion. A recombinant small hairpin RNA expression vector carrying ADAM10 was constructed and then transfected into the HepG2 human HCC cell line. In vitro cell proliferation, cell cycle, cell migration and cell invasion, and in vivo tumor growth were determined following the downregulation of ADAM10 by RNA interference. The results revealed that downregulation of ADAM10 expression in HepG2 tumor cells using the RNA silencing approach significantly suppressed cell proliferation, cell migration and cell invasion in vitro, and tumor growth in vivo. Furthermore, ADAM10 silencing was able to significantly reduce constitutive phosphorylation of phosphoinositide 3-kinase (PI3K) and Akt, which implies that ADAM10 is, at least partially, involved in the activation of the PI3K/Akt signaling pathway. These results suggest that ADAM10 is important in regulating the proliferation and metastasis of HCC. Thus, ADAM10 is a promising therapeutic target for the prevention of tumor metastases in HCC.