Enhanced anticancer activity of a protein phosphatase 2A inhibitor on chemotherapy and radiation in head and neck squamous cell carcinoma
| Autor: | Xi Yang, Yong-xiang Yuan, Cong Yu, Dong-wang Zhu, Zhiyuan Zhang, Lai-ping Zhong, Jin-ke Qiao, Lizhen Wang |
|---|---|
| Rok vydání: | 2015 |
| Předmět: |
Male
Cancer Research Blotting Western Mice Nude Piperazines Mice Antineoplastic Combined Chemotherapy Protocols Tumor Cells Cultured medicine Animals Humans Protein Phosphatase 2 Enzyme Inhibitors Protein kinase B Cell Proliferation Cisplatin Mice Inbred BALB C biology Chemistry Cell Cycle Chemoradiotherapy Protein phosphatase 2 Cell cycle Bridged Bicyclo Compounds Heterocyclic medicine.disease Xenograft Model Antitumor Assays Head and neck squamous-cell carcinoma Oncology Head and Neck Neoplasms Cancer cell Carcinoma Squamous Cell Cancer research biology.protein Phosphorylation Mdm2 Fluorouracil Signal Transduction medicine.drug |
| Zdroj: | Cancer Letters. 356:773-780 |
| ISSN: | 0304-3835 |
| DOI: | 10.1016/j.canlet.2014.10.024 |
| Popis: | The aim of this study is to eliminate more cancer cells by promoting them from quiescence into cell cycle or by changing their molecular events, leading them to be sensitive to radiation or chemotherapy. Protein phosphatase 2A plays an important role in many cellular functions and regulates various biological processes. It is unclear that LB1, which is an inhibitor of protein phosphatase 2A, has enhanced anticancer activity on chemotherapy (cisplatin and 5-fluorourcil) and radiation in head and neck squamous cell carcinoma (HNSCC). Herein, we performed both in vitro and in vivo studies to determine the anticancer activity of LB1 on chemotherapy and radiation in HNSCC, with detection of p53 expression, AKT and MDM2 phosphorylation. In vitro studies indicated that, LB1 could significantly enhance the cytotoxicity of cisplatin, 5-fluorourcil, and radiation; LB1 could also significantly enhance the treatment effect of cisplatin in nude mice. The anticancer activity of LB1 was mediated by increased AKT phosphorylation and decreased p53 expression with increased MDM2 phosphorylation, especially when combined with cisplatin. Our data suggest a strategy of improving treatment effect through the enhanced anticancer activity of LB1 on cisplatin-based chemotherapy and radiation in HNSCC. |
| Databáze: | OpenAIRE |
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