| RRC ID |
52423
|
| 著者 |
Tsubaki M, Takeda T, Asano RT, Matsuda T, Fujimoto SI, Itoh T, Imano M, Satou T, Nishida S.
|
| タイトル |
Rebamipide suppresses 5-fluorouracil-induced cell death via the activation of Akt/mTOR pathway and regulates the expression of Bcl-2 family proteins.
|
| ジャーナル |
Toxicol In Vitro
|
| Abstract |
Oral mucositis is a common adverse effect of chemotherapy that limits the required dose of chemotherapeutic agents. Numerous attempts to mitigate chemotherapy-induced oral mucositis have failed to identify an appropriate treatment. Recently, it has been indicated that rebamipide prevents chemoradiotherapy-induced oral mucositis in patients. However, the details of the underlying mechanism involved in the cytoprotective effect of rebamipide remain obscure. In the present study, we investigated the mechanism behind rebamipide cytoprotective effect in the oral mucosa using primary normal human oral keratinocytes (NHOK cells). We found that rebamipide prevented 5-fluorouracil (5-FU)-induced cell death in NHOK cells. In addition, rebamipide increased the levels of phosphorylated Akt and mTOR, enhanced the Bcl-2 and Bcl-xL expressions, and suppressed the expression of Bax and Bim. This is in contrast to 5-FU-induced suppression of Akt and mTOR activation, Bcl-2 and Bcl-xL expressions, and the enhanced expression of Bax and Bim. These findings suggest that rebamipide can potentially be used for the protection of oral mucosa from chemotherapy-induced mucositis. This is the first study that elucidates the specific molecular pathway for the cytoprotective effect of rebamipide.
|
| 巻・号 |
46
|
| ページ |
284-293
|
| 公開日 |
2018-2-1
|
| DOI |
10.1016/j.tiv.2017.10.019
|
| PII |
S0887-2333(17)30316-8
|
| PMID |
29054700
|
| MeSH |
Alanine / analogs & derivatives*
Alanine / pharmacology
Animals
Antimetabolites / toxicity
Antioxidants / toxicity
Cell Death / drug effects
Cell Survival
Fluorouracil / toxicity*
Gene Expression Regulation / drug effects
Humans
Keratinocytes / drug effects*
Mucositis
Proto-Oncogene Proteins c-akt / genetics
Proto-Oncogene Proteins c-akt / metabolism*
Proto-Oncogene Proteins c-bcl-2 / genetics
Proto-Oncogene Proteins c-bcl-2 / metabolism*
Quinolones / pharmacology*
TOR Serine-Threonine Kinases
|
| IF |
2.959
|
| 引用数 |
1
|
| リソース情報 |
| ヒト・動物細胞 |
CACO-2(RCB0988)
COLO205(RCB2127) |
