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Dang L.,Zhengzhou University | Wen F.,Zhengzhou University | Wen F.,Institute of Henan Province | Yang Y.,Zhengzhou University | And 13 more authors.
International Journal of Molecular Medicine | Year: 2014

Comprehensive treatment based on chemotherapy is regarded as the first-line treatment for patients with unresectable or metastatic esophageal squamous cell carcinoma (ESCC). However, chemoresistance is common among patients with ESCC. Therefore, there is a need to explore new therapeutic strategies or adjuvant drugs. One promising possibility is to use dietary agents that can increase tumor cell sensitivity to drugs. In this study, we initially investigated the antitumor activity of proteasome inhibitor MG132 in vitro and in vivo. Effects of MG132 on the enhancment of the anticancer functions of cisplatin were then investigated in human esophageal cancer EC9706 cells in relation to apoptosis and cell signaling events. Exposure of cells to MG132 resulted in a marked decrease in cell viability in a dose- and time-dependent manner. Administration of MG132 markedly inhibited tumor growth in the EC9706 xenograft model. MG132 significantly enhanced cisplatin-induced apoptosis in association with the activation of caspase-3 and -8. These events were accompanied by the downregulation of NF-κB, which plays a key role in cell apoptosis. Taken together, these findings demonstrate a novel mechanism by which proteasome inhibitor MG132 potentiates cisplatin-induced apoptosis in human ESCC and inhibitory activity of tumor growth of the EC9706 xenograft model.

Zhao J.,Zhengzhou University | Zhao J.,Key Thoracic Tumour Experimental Laboratory of Zhengzhou | Li X.,Zhengzhou University | Li X.,Key Thoracic Tumour Experimental Laboratory of Zhengzhou | And 12 more authors.
OncoTargets and Therapy | Year: 2016

Background: YAP1, the nuclear effector of the Hippo pathway, has become an attractive target for treatment of malignancies and is a candidate oncogene in esophageal cancer (EC). We hypothesized that knockdown of YAP1 could suppress EC and could be used for targeted therapy. However, there are few reports of the effect of YAP1 knockdown in EC. Materials and methods: Quantitative real-time polymerase chain reaction and Western blot assays were performed to determine the expression levels of YAP1 mRNA and protein in primary EC tissue samples, EC cell lines, and controls. Immunohistochemistry was also performed to detect YAP1 protein expression in primary EC tumor and matched nontumor control tissues. YAP1-knockdown cell lines were constructed using short-hairpin RNA, and MTT, flow cytometry, and transwell chamber assays were used to analyze the effect of YAP1 knockdown on EC cell proliferation, apoptosis, and invasion. In vivo tumor formation assays were used to investigate the antitumor effect of YAP1 knockdown. Results: We found that YAP1 mRNA and protein were upregulated in EC and that YAP1 expression correlated significantly with metastasis and tumor stage. We also found that YAP1 knockdown repressed cell proliferation and invasion and promoted apoptosis of EC cell lines. In addition, animal experiments revealed that YAP1 knockdown suppressed the growth of esophageal tumors in vivo. Conclusion: Collectively, these data confirm our hypothesis that YAP1 knockdown suppresses EC and suggest that YAP1 knockdown could be exploited in the targeted gene therapy of EC in the future. © 2016 Zhao et al.

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