| Autor: |
Wu Bin, Li Ji, Huang Damao, Wang Weiwei, Chen Yu, Liao Youxiang, Tang Xiaowei, Xie Hongfu, Tang Faqing |
| Jazyk: |
angličtina |
| Rok vydání: |
2011 |
| Předmět: |
|
| Zdroj: |
BMC Cancer, Vol 11, Iss 1, p 527 (2011) |
| Druh dokumentu: |
article |
| ISSN: |
1471-2407 |
| DOI: |
10.1186/1471-2407-11-527 |
| Popis: |
Abstract Background Ezrin is highly expressed in skin cancer and promotes tumor metastasis. Ezrin serves as a promising target for anti-metastasis therapy. The aim of this study is to determine if the flavonoid bacailein inhibits the metastasis of skin cancer cells through Ezrin. Methods Cells from a cutaneous squamous carcinoma cell line, A431, were treated with baicalein at 0-60 μM to establish the non-cytotoxic concentration (NCC) range for baicalein. Following treatment with baicalein within this range, total Ezrin protein (both phosphorylated and unphosphorylated forms) and phosphorylated-Ezrin (phos-Ezrin) were detected by western blotting, and Ezrin RNA was detected in A431 cells using reverse transcription-polymerase chain reaction (RT-PCR). Thereafter, the motility and invasiveness of A431 cells following baicalein treatment were determined using wound-healing and Boyden chamber invasion assays. Short-interfering RNA (si-RNA) specifically targeting Ezrin was transfected into A431 cells, and a si-RNA Ezrin-A431 cell line was established by G418 selection. This stable cell line was transiently transfected with Ezrin and mutant Ezrin plasmids, and its motilityand invasiveness was subsequently determined to clarify whether bacailein inhibits these processes through Ezrin. Results We determined the range of NCCs for baicalein to be 2.5-40 μM in A431 cells. Baicalein displayed a dose- and time-dependent inhibition of expressions of total Ezrin and phos-Ezrin within this range NCCs. In addition, it exerted this inhibitory effect through the reduction of Ezrin RNA transcript. Baicalein also inhibited the motility and invasiveness of A431 skin carcinoma cells within the range of NCCs, in a dose- and time-dependent manner. A431 cell motility and invasiveness were inhibited by 73% and 80% respectively when cells were treated with 20 μM baicalein. However, the motility and invasiveness of A431 cells containing the Ezrin mutant were not effectively inhibited by baicalein. Conclusions Baicalein reduces the migration and invasiveness of A431 cells through the inhibition of Ezrin expression, which leads to the suppression of tumor metastasis. |
| Databáze: |
Directory of Open Access Journals |
| Externí odkaz: |
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