| Project/Area Number |
09670195
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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 |
Human pathology
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| Research Institution | Fukushima medical University School of Medicine |
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Principal Investigator |
FUKUDA Takeaki Department of Pathology Fukushima Medical University, Associate Professor, 医学部・病理二, 助教授 (20199235)
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| Co-Investigator(Kenkyū-buntansha) |
KAKIHARA Toshio Department of Pediatrics Niigata University, School of medicine, Assistant, 医学部・小児科, 助手 (70262433)
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| Project Period (FY) |
1997 – 1998
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| Project Status |
Completed (Fiscal Year 1998)
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| Budget Amount *help |
¥600,000 (Direct Cost: ¥600,000)
Fiscal Year 1998: ¥600,000 (Direct Cost: ¥600,000)
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| Keywords | Drug resistance / Transcription factor / apoptosis / heat shock protein / NF-KB / 熱ショック蛋白 / TNFα |
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| Research Abstract |
In this study the overcome of drug resistance by some agents having a inhibitory effect on the expression of transcription factors (TFs) has been evaluated on various types of drug resistant human cancer cell lines. In drug-sensitive cell lines, the activity of NF-kappa B was induced by tumor necrosis factor alpha and interferon gamma and apoptosis was induced. Pentoxyfilline, aspirin and acetyl cysteine can inhibit the activity of NF-kappa B but apoptosis was induced. In drug resistant cell lines, the activity of NF-kB was elevated under normal culture condition. It was inhibited by the agents described above and moderate overcome of drug resistance was achieved. In AraC resistant cell lines, NF-kB as well as Sp-1 and Sp-2 were activated, suggesting an important role in AraC resistance. Pentoxyfilline and FK506 inhibited the activity of these TFs but levels of drug resistance was slightly overcame. In drug resistant cell lines, elevated expression of heat shock proteins (HSPs) was observed in both cytoplasm and nucleus, suggesting a role in drug resistance with unknown mechanism. Pentoxyfilline and FK506 decreased the expression of HSPs and enhanced anticancer effect slightly. Further study is needed to elucidate whether these agents affect HSPs directly or through TBS.The combination with anticancer drugs and agents inhibiting TFs may be effective for overcome drug resistance.
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