Inhibitory Effect of Sorafenib on Growth of Human Esophageal Cancer Cells EC9706
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Graphical Abstract
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Abstract
Objective To investigate the inhibitory effect of sorafenib on the growth of esophageal cancer cells EC9706 in vitro and its mechanism. Methods Effect of sorafenib on the expression of MMP-2, MMP-9, TIMP1, AKT and Bcl-2 were detected by qRT-PCR. Effect of sorafenib on the expression of AKT, p-AKT, Bcl-2, MMP-2 and TIMP1 were detected by Western blot. Cell apoptosis/necrosis induced by sorafenib were observed by Hoechst/PI staining. The inhibitory effect of sorafenib on EC9706 cells migration was observed by cell scratch test. Results qRT-PCR data showed downregulation of MMP-2, MMP-9, AKT, Bcl-2 and upregulation of TIMP1 mRNA, compared with the control group(P<0.05); furthermore, Western blot analysis revealed the expression of MMP-2, AKT, p-AKT, Bcl-2 proteins were downregulated and TIMP1 protein expression was upregulated in the sorafenib groups compared with the control group(P<0.05).Sorafenib was found not only to inhibit the migration of EC9706 cells in vitro by cell scratch test, but also to promote cells apoptosis in vitro by Hoechst/PI apoptosis/necrosis detection(P<0.05). Conclusion Sorafenib could upregulate the expression of TIMP1, downregulate the expression of MMP-9, AKT, MMP-2 and Bcl-2,and inhibit the migration and promote apoptosis/necrosis of esophageal cancer cells EC9706. These may be its anticancer mechanism.
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