Multidrug-resistance of cancer cells and their recovery by regulating expressions of DAP kinase-related molecules
Project/Area Number |
20591959
|
Research Category |
Grant-in-Aid for Scientific Research (C)
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Allocation Type | Single-year Grants |
Section | 一般 |
Research Field |
Obstetrics and gynecology
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Research Institution | Wakayama Medical University |
Principal Investigator |
TANAKA Tetsuji Wakayama Medical University, 医学部, 准教授 (80275255)
|
Co-Investigator(Kenkyū-buntansha) |
MATSUOKA Toshihide 和歌山県立医科大学, 医学部, 助教 (70464675)
UTSUNOMIYA Tomoko 和歌山県立医科大学, 医学部, 博士研究員 (60382355)
IKEJIMA MiwA 和歌山県立医科大学, 医学部, 助教 (70433349)
|
Project Period (FY) |
2008 – 2010
|
Project Status |
Completed (Fiscal Year 2010)
|
Budget Amount *help |
¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2010: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2009: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2008: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
|
Keywords | 婦人科腫瘍学 / 抗癌剤 / 抗癌剤耐性 / death-associated protein kinase / メチル化 / エビジェネティックス / エピジェネティックス |
Research Abstract |
This study was performed to investigate a possibility of anticancer molecular targeting therapy of Death-associated Protein Kinase (DAPK). (1) DAPK knockdown regulated anticancer drug-sensitivities of cancer cells. i) Targeted DAPK knockdown by DAPK-specific siRNA transfections enhanced the Fas/TRAIL-mediated apoptotic susceptibility in human endometrial adenocarcinoma cells. These results indicate that DAP kinase can be a powerful candidate of anticancer molecularly targeting therapy for human endometrial cancer patients. ii) Targeted DAPK knockdown induced apoptosis in human uterine carcinosarcoma cells and human uterine leiomyosarcoma cells. The results suggest that DAP kinase can be a candidate of anticancer molecularly targeting therapy for uterine carcinosarcoma and sarcoma patients in addition to endometrial adenocarcinoma patients. iii) Targeted DAPK knockdown enhanced 5FU-sensitivity but not VP16-sensitivity, and enhanced partially CDDP-sensitivity in human endometrial adenocarcinoma cells. However, it did not improve their 5FU-sensitivities in the 5FU-resistant cells. These results indicate that the molecular targeting therapy of DAPK can be applied to restricted anticancer chemotherapies. (2) Regulation of DAPK expression by demethylation improved some of anticancer drug-sensitivities in anticancer drug-resistant cervical cancer cells.
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Report
(4 results)
Research Products
(33 results)