2001 Fiscal Year Final Research Report Summary
Fundamental study on molecular chaperone cancer therapy
| Project/Area Number |
12670899
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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 |
Radiation science
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| Research Institution | Nara Medical University |
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Principal Investigator |
OHNISHI Ken Nara Medical University, Department of Biology, Associate Professor, 医学部, 助教授 (50152195)
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| Project Period (FY) |
2000 – 2001
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| Keywords | molecular chaperone / glycerol / radiation / hypothermia / anti-cancer agent / apoptosis / gene transfection / p53 |
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| Research Abstract |
The aim of this study is to develop new cancer therapy, which is based on a chemical chaperone (glycerol) to change conformation of mutant p53 (mp53) protein to wild-type p53 (wtp53) protein and restore the function of wtp53. Transfection with wtp53 to p53-null cells increased the thermo sensitivity and enhanced heat-induced apoptosis.Human annalistic thyroid carcinoma cells (8305c) transected with temperature sensitive mp53 showed radio-, heat- or CDDP-sensitivity under culture condition inducing wtp53. Human aqueous cell carcinoma (SAS/mp53) cells transected with mp53 were resistant to X-ray or CDDP compared with the control cells having normal function of p53 (SAS/neo). However, SAS/mp53 cells became sensitive to X-ray or CDDP after X-ray or CDDP treatment in the presence of glycerol, while that of SAS/neo cells did not. X-ray or CDDP-induced apoptosis was suppressed in SAS/mp53 cells, whereas X-ray or CDDP treatment combined with glycerol induced efficient DNA fragmentation and apoptotic bodies in SAS/mp53 cells. Growth delay was observed in SAS/mp53 tumors transplanted in nude mice when they were treated with CDDP in the presence of glycerol. From these results, radiation and chemical therapies combined chemical chaperone therapy might improve the outcome of cancer therapies.
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