权益分类	功能权益	普通用户	{{item.name}}会员
{{category.name}}	{{benefitItem.name}}

Multidrug-resistance of cancer cells and their recovery by regulating expressions of DAP kinase-related molecules

癌细胞的多药耐药性及其通过调节DAP激酶相关分子表达的恢复

基本信息

批准号：
20591959
负责人：
TANAKA Tetsuji
金额：
$ 2.91万
依托单位：
Wakayama Medical University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2008
资助国家：
日本
起止时间：
2008 至 2010
项目状态：
已结题

项目摘要

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.

本研究旨在探讨死亡相关蛋白激酶（DAPK）作为抗癌分子靶向治疗的可能性。(1)DAPK敲低调节癌细胞的抗癌药物敏感性。i）通过DAPK特异性siRNA转染的靶向DAPK敲低增强了人子宫内膜腺癌细胞中Fas/TRAIL介导的凋亡易感性。这些结果表明，DAP激酶可能是一个强有力的候选人的抗癌分子靶向治疗人类子宫内膜癌患者。ii）靶向DAPK敲低诱导人子宫癌肉瘤细胞和人子宫平滑肌肉瘤细胞中的细胞凋亡。结果表明，DAP激酶可作为子宫内膜腺癌患者以外的子宫癌肉瘤和肉瘤患者的抗癌分子靶向治疗的候选药物。iii）靶向DAPK敲低增强人子宫内膜腺癌细胞中的5 FU敏感性，但不增强VP 16敏感性，并且部分增强CDDP敏感性。然而，它并没有提高其在5 FU耐药细胞中的5 FU敏感性。这些结果表明，DAPK的分子靶向治疗可应用于限制性抗癌化疗。(2)通过去甲基化调节DAPK表达可提高宫颈癌耐药细胞对某些抗癌药物的敏感性。