In this study, we have shown that the expression of the kinase CDK11p110 is commonly increased in ESCC cell lines and tissues

In this study, we have shown that the expression of the kinase CDK11p110 is commonly increased in ESCC cell lines and tissues. by pCDH vector-transfected cells (p 0.05). At the termination of the experiment, the net weight of tumors formed by CDK11p110-overexpressing EC109 cells was also significantly increased compared with that of tumors formed by the control and pCDH-expressing cells (p 0.01; Figure 6(d)). Moreover, immunohistochemical staining indicated a significant increase in the expression of CDK11p110 and the Ki67 cell proliferation index in tumors formed by EC109 cells stably overexpressing CDK11p110 Buclizine HCl (Figure 6(e)). Conversely, the increase in the volume of tumors formed Corin from control or pLKO.1-transfected EC109 cells was strongly suppressed in EC109 cells with stable shRNA-mediated knockdown of CDK11p110 (p 0.001; Figure 6(f,g)). Similarly, at the termination of the experiment, the net weight of Buclizine HCl tumors formed by CDK11p110-knockdown cells was also dramatically decreased compared with that of tumors formed by control or pLKO.1-transfected cells (p 0.001; Figure 6(h)). Additionally, immunohistochemical staining showed a significant decrease in the expression of CDK11p110 and Ki67 in tumors formed by stable shRNA-mediated knockdown cells (Figure 6(e)), indicating that the tumor suppressive effect was exerted by CDK11p110 depletion. Overall, these data support an important role of CDK11p110 in controlling Buclizine HCl ESCC cell formation and progression EC109 xenograft model confirmed the critical role of CDK11p110 in ESCC cell tumorigenicity. (a) Stable CDK11p110 overexpression or knockdown EC109 xenograft model in athymic nude mice. (b) Subcutaneous tumor growth of CDK11p110-overexpressing EC109 cells, vector pCDH-transfected cells and control (untransfected) cells in nude mice. *P 0.05, against pCDH group. NS, not significant. The data are the means SD (n = 7/group). (c) Photographs of the excised EC109 tumors from all groups of mice, including those inoculated with control, pCDH- or pCDH-CDK11p110-transfected EC109 cells. (d) Tumor weights in different groups of mice inoculated with control, pCDH- and pCDH-CDK11p110-transfected EC109 cells. **P 0.01 compared with the pCDH EC109 cell groups. NS, not significant. The data are the means SD (n = 7/group). (e) The expression of CDK11p110 and of the tumor proliferation marker Ki67 in stable CDK11p110-overexpressing EC109 subcutaneous xenografts were examined by immunohistochemistry. Scale bar: 20 m. (f) Subcutaneous tumor growth of CDK11p110-knockdown EC109 cells, pLKO.1-transfected cells and control cells in nude mice. ***P 0.001, versus the pLKO.1 group. NS, not significant. The data are the means SD (n = 7/group). (g) Photographs of the excised EC109 tumors from all groups of mice including those inoculated with control, pLKO.1-, pLKO.1-shCDK11p110-1- and pLKO.1-shCDK11p110-2-transfected EC109 cells. (h) Tumor weights in different groups inoculated with control, pLKO.1- and pLKO.1-shCDK11p110-1- and pLKO.1-shCDK11p110-2-transfected EC109 cells. ***P 0.001, versus the pCDH-EC109 group. Buclizine HCl NS, not significant. The data are the means SD (n = 7/group). (i) Confirmation of CDK11p110 expression and Ki67 staining in stable CDK11p110-knockdown EC109 subcutaneous xenografts by immunohistochemistry. Scale bar: 20 m. For all data, comparisons between three groups were analyzed by one-way ANOVA and comparisons between two groups were performed by students t test. Discussion More than 50% of ESCC patients present with unresectable or metastatic disease at the time of diagnosis [4]. Unfortunately, there is a serious deficiency of effective clinical therapy strategies targeting ESCC, and most of the current research in esophageal cancer focuses on esophageal adenocarcinoma and gastroesophageal junction cancer [4,30C32]. Accumulating studies have demonstrated that CDKs are overexpressed or activated in cancer, and targeting CDKs in tumor cells has become a promising therapeutic strategy against cancer [8,9]. As a member of CDK family, CDK11p110 in particular is reported to be critical for the growth and proliferation of some types of cancer cells [33]. However,.