Inhibitory effect of heat shock proteins in apoptosis in acquisition of anticancer drug resistance
| Project/Area Number |
11670182
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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 Fukushima Medical University School of Medicine, Associate professor, 第二医理, 助教授 (20199235)
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| Co-Investigator(Kenkyū-buntansha) |
KAKIHARA Toshio Niigata University School of Medicine, Assistant professor, 医学部・小児科, 講師 (70262433)
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| Project Period (FY) |
1999 – 2001
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| Project Status |
Completed (Fiscal Year 2000)
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| Budget Amount *help |
¥3,400,000 (Direct Cost: ¥3,400,000)
Fiscal Year 2000: ¥900,000 (Direct Cost: ¥900,000)
Fiscal Year 1999: ¥2,500,000 (Direct Cost: ¥2,500,000)
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| Keywords | Shock proteins / apoptosis / drug resistance / oligoprobe / overcome of drug resistance / アポトーシス / anti-sense / 免疫抑制剤 |
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| Research Abstract |
Based on the our previous research, heat shock proteins (HSPs) play a role in acquisition of drug resistance, regardless of spieces of anticancer drugs. The aim of this research is to elucidate the regulation mechanism of expression of HSPs and the role of HSPs in apoptosis pathway by RT-PCR and gel-shift methods. Furthermore anti-sense oligoprobes to HSPs and HSE have been examined to estimate the effect of overcome of drug resistance. The levels of HSE in drug resistance cell lines have not been altered in each cell line, regardless of differentiated expression of HSPs. This finding suggests that HSF but not HSE plays a role in expression of HSPs, although the exact mechanism can not be elicited in this study. To estimate the overcome effect of anti-sense oligoprobe for HSP or HSE, three of synthesized anti-sense oligoprobes, especially anti-sense oligoprobe to HSP27, showed an evident overcome effect on drug resistance. The anti-sense oligoprobe to HSP27 inhibited the expression of mRNA of HSP27 and partilly overcame the drug resistance. Interestingly this probe could overcome the TGF-β resistance as well as anticancer resistance in HACC-TG cell line which was resistant to TGF-β as well as various anti-cancer drugs. Furthermore combination with this probe and cerulenin which was an inhibitor of fatty acid snythetase, suggesting some roles of HSP27 in lipid synthesis. The other two could inhibit of expression of mRNA of HSPs but lacked the overcome effect on drug resistance. Transfection of various HSP genes failed to induce genes associated with apoptosis. However, baxmRNA was diminished in the cells transfected with HSP70 or HSP27 genes, compared with that of the parental cells. However, the exact target points of HSPs can not be elucidated in apoptosis pathway.
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Report
(3 results)
Research Products
(6 results)
