Laboratory of Renal Carcinoma, Ningbo Yinzhou No. 2 Hospital, Ningbo 315100, Zhejiang, P.R., China.
Acta Pharm. 2018 Dec 1;68(4):497-506. doi: 10.2478/acph-2018-0033.
Our previous reports showed that the cyclic-AMP-response element-binding protein (CREB) served as a proto-oncogene in the process of tumorigenesis and mediated the growth and metastatic activity of renal cancer cells. Our study, therefore, explored the role of CREB in sorafenib- -inhibited cell proliferation, migration and invasion. Renal cancer cells were cultured in medium containing sorafenib for 12, 24, 48 and 72 h. The MTT assay was used to study the cytotoxic effects of sorafenib. Cell invasion and migration were assayed in wound healing and transwell experiments, respectively. Protein expression levels were evaluated by western blotting. The results show that sorafenib treatment decreased cell viability in a dose- and time-dependent manner. Sorafenib inhibited cell migration and invasion and decreased the expression of MMP-2 and MMP-9. Moreover, addition of the recombinant plasmid pCI-neo/ CREB (PN) reversed the sorafenib-induced inhibition of cell proliferation, migration and invasion. These results show that CREB is associated with the sorafenib-induced inhibition of proliferation, migration and invasion.
我们之前的报告表明,环腺苷酸反应元件结合蛋白(CREB)在肿瘤发生过程中充当原癌基因,并介导肾癌细胞的生长和转移活性。因此,我们的研究探讨了 CREB 在索拉非尼抑制细胞增殖、迁移和侵袭中的作用。将肾癌细胞在含有索拉非尼的培养基中培养 12、24、48 和 72 小时。采用 MTT 法研究索拉非尼的细胞毒性作用。分别通过划痕愈合实验和 Transwell 实验检测细胞侵袭和迁移。通过 Western blot 评估蛋白表达水平。结果表明,索拉非尼处理呈剂量和时间依赖性地降低细胞活力。索拉非尼抑制细胞迁移和侵袭,并降低 MMP-2 和 MMP-9 的表达。此外,添加重组质粒 pCI-neo/CREB(PN)逆转了索拉非尼诱导的细胞增殖、迁移和侵袭抑制。这些结果表明,CREB 与索拉非尼诱导的增殖、迁移和侵袭抑制有关。