Development of molecular targeting therapy against stability of p27^<Kip1> protein in oral squamous cell carcinoma.
| Project/Area Number |
17592089
|
|---|
| Research Category |
Grant-in-Aid for Scientific Research (C)
|
| Allocation Type | Single-year Grants |
|---|
| Section | 一般 |
|---|
| Research Field |
Surgical dentistry
|
|---|
| Research Institution | The University of Tokushima |
|---|
Principal Investigator |
HARADA Koji The University of Tokushima Graduate School, Institute of Health Bioscience, Assistant lecturer, 大学院ヘルスバイオサイエンス研究部, 助手 (60253217)
|
|---|
| Project Period (FY) |
2005 – 2006
|
| Project Status |
Completed (Fiscal Year 2006)
|
| Budget Amount *help |
¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 2006: ¥1,700,000 (Direct Cost: ¥1,700,000)
Fiscal Year 2005: ¥1,800,000 (Direct Cost: ¥1,800,000)
|
|---|
| Keywords | Proteasome inhibitor / p27^<Kip1> / Jab1 / Skp2 / Autophage / p27^<Kipl> / p27^<Kip1> / TS-1 / 口腔扁平上皮癌 |
|---|
| Research Abstract |
The Jab1 expression was investigated by immunohistochemistry in biopsy samples from 102 OSCC patients who were treated by UFT in combination with radiation. Associations of each expression with clinicopathological characteristics and patient survival were also analyzed. A significant association was found between Jab1 expression and cervical lymph node metastasis (p=0.0004), stage of disease (p=0.0011), therapeutic effect (p=0.0133) and patient outcome (p=0.0095). The 5-year survival rates of Jab1 high and low expression tumors were 53.0 % and 80.6 %, respectively, and this difference was significant (p=0.0053) by log-rank test. Multivariate analysis revealed that reduced term survival was related to high levels of Jab1 expression (p=0.0082). These results suggest that Jab1 may be a useful prognostic factor in OSCC patients treated by UFT in combination with radiation.
Proteasome inhibitor 1 (PSI1; 10 ng-100 μg/ml) could exert growth inhibitory effects on OSCC cells through suppressing the degradation of p27^<Kip1> protein. In addition, PSI1 could induce apoptosis through the activation of caspase-8, caspase-9 and caspase-3, and that might induce autophage through the induction of Beclin-1 and microtuble associated protein 1 light chain 3 (LC3). Moreover, PSI1 could enhance the anticancer effects of 5-FU and CDDP, but not TXT in vitro. Furthermore, PSI1 (0.1-1mg/kg/day) could exert antitumor effects on nude mice tumors through suppressing the degradation of p27^<Kip1> protein, and PSI could enhance the antitumor effects of 5-FU, TS-1 and CDDP, but not TXT in vivo.
These results indicate that PSI1 can exert antitumor effects through suppressing the degradation of p27^<Kip1> protein, and we may be able to develop the molecular targeting therapy against stability of p27^<Kip1> protein in oral squamous cell carcinoma.
|
Report
(3 results)
Research Products
(30 results)
