| RRC ID |
64023
|
| 著者 |
Kamigaki M, Sasaki T, Serikawa M, Inoue M, Kobayashi K, Itsuki H, Minami T, Yukutake M, Okazaki A, Ishigaki T, Ishii Y, Kosaka K, Chayama K.
|
| タイトル |
Statins induce apoptosis and inhibit proliferation in cholangiocarcinoma cells.
|
| ジャーナル |
Int J Oncol
|
| Abstract |
Given the poor prognosis for cholangiocarcinoma, new and effective treatments are urgently needed. HMG-CoA reductase inhibitors (statins) reportedly exert anticancer effects in a variety of diseases, but there have been no reports of these effects in cholangiocarcinoma. In this study, we investigated the utility of statins for cholangiocarcinoma treatment. Proliferation suppression by pitavastatin and atorvastatin was investigated in the human cholangiocarcinoma cell lines HuCCT1 and YSCCC while changes in the cell cycle and intracellular signals were examined by FACS and Western blotting, respectively. Additive proliferation suppression by statins and pre-existing anticancer drugs was also investigated. HuCCT1 and YSCCC cell proliferation was dramatically suppressed by incubation with statins for 72 h or longer. Cell cycle analysis revealed a reduction in the G2M fraction and an increase in the sub-G1 fraction in statin-treated cells, while Western blotting showed increased levels of cleaved caspase-3 and a reduction in p-ERK. Furthermore, statins in combination with gemcitabine, cisplatin and 5-FU showed additive proliferation suppression. In this study, treatment of human cholangiocarcinoma cells with statins induced apoptosis via suppression of the classical MAPK pathway. Together, these results suggest that statins may be a new cholangiocarcinoma treatment option that could potentially enhance the anticancer effect of pre-existing anticancer drugs.
|
| 巻・号 |
39(3)
|
| ページ |
561-8
|
| 公開日 |
2011-9-1
|
| DOI |
10.3892/ijo.2011.1087
|
| PMID |
21687941
|
| MeSH |
Apoptosis / drug effects*
Atorvastatin
Caspase 3 / metabolism
Cell Cycle / drug effects
Cell Differentiation / drug effects
Cell Growth Processes / drug effects
Cell Line, Tumor
Cholangiocarcinoma / drug therapy*
Cholangiocarcinoma / pathology*
Extracellular Signal-Regulated MAP Kinases / metabolism
Female
Heptanoic Acids / pharmacology
Humans
Hydroxymethylglutaryl-CoA Reductase Inhibitors / pharmacology*
Male
Neoplastic Stem Cells / drug effects*
Neoplastic Stem Cells / pathology
Pyrroles / pharmacology
Quinolines / pharmacology
|
| IF |
3.899
|
| リソース情報 |
| ヒト・動物細胞 |
HuCCT1(RCB1960)
YSCCC(RCB1549) |
