| RRC ID |
64615
|
| 著者 |
Higashi T, Hayashi H, Kitano Y, Yamamura K, Kaida T, Arima K, Taki K, Nakagawa S, Okabe H, Nitta H, Imai K, Hashimoto D, Chikamoto A, Beppu T, Baba H.
|
| タイトル |
Statin attenuates cell proliferative ability via TAZ (WWTR1) in hepatocellular carcinoma.
|
| ジャーナル |
Med Oncol
|
| Abstract |
Diabetes and obesity are associated with non-alcoholic steatohepatitis and an increased incidence of hepatocellular carcinoma (HCC). TAZ and YAP are equivalently placed downstream effectors of the Hippo pathway with oncogenic roles in human cancers. Statins are commonly used to patients with metabolic problems as hypercholesterolemia. Statins also have anti-cancer properties, and the cross-talk between mevalonate pathway and Hippo pathway was known. The aim of this study is to confirm the statin's anti-cancer effects on HCC cells and its survival benefits in HCC patients with curative surgery. TAZ expression level in HCC cell lines was analyzed by western blot. Two cell lines (HLF and HuH1) were used in this study. Then the mechanism of statin's anti-proliferative effect was examined in HLF and HuH1 cells. In clinical setting, overall survival and recurrence-free survival (RFS) rate were examined in comparison between statin intake and statin non-intake group. The proliferation assay using four different statins (atorvastatin, pravastatin, fluvastatin, simvastatin). Simvastatin and fluvastatin showed very strong growth suppressive effects, and induced apoptosis in HLF cells, but not HuH1 cells. TAZ expression was suppressed in HLF cells by fluvastatin and simvastatin treatment. The similar change pattern was confirmed in p-ERK1/2 and ERK. In HuH1 cells, such expression change was not confirmed. In clinical setting, statin intake was significantly associated with longer RFS in the HCC patients with hepatectomy (P = 0.038). The statin had the anti-proliferative effects and induced apoptosis in HCC cells and improved the prognosis of HCC patients.
|
| 巻・号 |
33(11)
|
| ページ |
123
|
| 公開日 |
2016-11-1
|
| DOI |
10.1007/s12032-016-0845-6
|
| PII |
10.1007/s12032-016-0845-6
|
| PMID |
27734263
|
| MeSH |
Acyltransferases
Adaptor Proteins, Signal Transducing / metabolism
Aged
Antineoplastic Agents / pharmacology
Antineoplastic Agents / therapeutic use*
Carcinoma, Hepatocellular / drug therapy*
Carcinoma, Hepatocellular / mortality
Carcinoma, Hepatocellular / pathology
Carcinoma, Hepatocellular / surgery
Cell Line, Tumor
Cell Proliferation / drug effects
Female
Gene Expression Regulation, Neoplastic
Hepatectomy
Hippo Signaling Pathway
Humans
Hydroxymethylglutaryl-CoA Reductase Inhibitors / therapeutic use*
Intracellular Signaling Peptides and Proteins / metabolism
Liver Neoplasms / drug therapy*
Liver Neoplasms / mortality
Liver Neoplasms / pathology
Liver Neoplasms / surgery
Male
Middle Aged
Neoplasm Recurrence, Local / drug therapy
Phosphoproteins / metabolism
Protein Serine-Threonine Kinases / metabolism
Trans-Activators
Transcription Factors / genetics
Transcription Factors / metabolism*
Transcriptional Coactivator with PDZ-Binding Motif Proteins
YAP-Signaling Proteins
|
| IF |
2.834
|
| リソース情報 |
| ヒト・動物細胞 |
Li-7(RCB1941) |
