| Project/Area Number |
17591750
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Obstetrics and gynecology
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| Research Institution | Sapporo Medical University |
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Principal Investigator |
ISHIOKA Shin Sapporo Medical University, 医学部, Assistant professor (90305219)
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| Co-Investigator(Kenkyū-buntansha) |
KOTA Umemura Sapporo Medical University, 医学部, Instructor (60404795)
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| Project Period (FY) |
2005 – 2007
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| Project Status |
Completed (Fiscal Year 2007)
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| Budget Amount *help |
¥2,850,000 (Direct Cost: ¥2,700,000、Indirect Cost: ¥150,000)
Fiscal Year 2007: ¥650,000 (Direct Cost: ¥500,000、Indirect Cost: ¥150,000)
Fiscal Year 2006: ¥700,000 (Direct Cost: ¥700,000)
Fiscal Year 2005: ¥1,500,000 (Direct Cost: ¥1,500,000)
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| Keywords | ovarian cancer / anti cancer drug / proteome / 臨床 |
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| Research Abstract |
To understand mechanisms of drug resistance in ovarian cancer, especially in clear cell cancer, we focused on the roles of anticancer drug-induced apoptosis pathways. We looked at Paclitaxel (PTX)-induced apoptosis in ovarian cancer cells by using both genomic and protemic techniques. The aim of this study was to characterize global changes of apoptosis-related proteins induced by PTX in ovarian cells so as to clarify the mechanism of anticancer drug resistance by using an antibody-based protein array.
An ovarian cancer cell line KF, and its PTX resistant clone KFTX, and clear cell cancer cell line TAYA were treated with PTX. After exposure to PTX, the induction of apoptosis was examined 'by internucleosomal DNA fragmentation. And with the use of protein array, changes in the protein expression were studied. Several antisense oligonucleotide against drug resistance-related genes were also used to study changes of protein expression.
With increased doses of PTX or CBDCA, an increase in apoptosis was noted in each cell line. Protein array and cDNA microaaray revealed that PTX treatment up-regulated expression of caspases and some stress reaction-related genes in KF, although most of them were unchanged or down-regulated in KFTX. bag-1 were markedly up-regulated in KFTX. Antisense oligonucleotide against bag-1 showed the recovery of sensitivity against PTX in KFTX. Bag-1 seemed to play an important role in acquirement of drug resistance. Immnohistochemistry also showed the importance of Bag-1 in acquirement of drug resistance in clear cell ovarian cancer. In other study, expression of adiponectin receptors were high in drug sensitive clear cell ovarian cancer. Expression of adiponectin in clear cell cancer seemed to be involved in the sensitivity' to anticancer drugs.
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