2005 Fiscal Year Final Research Report Summary
Apoptosis-related gene expression after irradiation, chemotherapy and hyperthermia in Oral cancer
| Project/Area Number |
15390620
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Surgical dentistry
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| Research Institution | Nara Medical University |
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Principal Investigator |
KIRITA Tadaaki Nara Medical University, Department of Oral and Maxillofacial Surgery, Professor, 医学部, 教授 (70201465)
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| Co-Investigator(Kenkyū-buntansha) |
OHNISHI Takeo Nara Medical University, Department of Biology, Professor, 医学部, 教授 (60094554)
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| Project Period (FY) |
2003 – 2005
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| Keywords | p53 / apoptosis / irradiation / hyperthermia / proteintip / glycerol / chemical-chaperon / cluster-analysis |
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| Research Abstract |
Irradiation, chemotherapy and hyperthermia is useful for the treatment of human head and neck cancer.
We used two kinds of cell lines of a human squamous cell carcinoma (SAS) with identical backgrounds of function except for the p53 protein, which are SAS/mp53 cells with mp53 and SAS/neo cells with wtp53. We previously reported that the heat sensitivity and frequency of apoptosis in SAS/neo cells were clearly high as compared with SAS/mp53 cells. In order to elucidate the expression of apoptosis-related proteins after heat treatment, we used protein microarray analysis. The expression of apoptosis-inhibitive proteins, such as Bcl-2, Bcl-xL, NF-кB, COX2,Stat3, IL6 and IKKα/1, were increased by heat treatment in SAS cells expressing mp53, but not in SAS cells with wtp53. It is suggested that heat-induced apoptosis was suppressed by these proteins in the mp53 cells. These findings strongly imply that p53 status is a useful candidate for a predictive indicator of the effectiveness in hyperthermic therapy.
Radiotherapy for oral squamous cell carcinomas is limited in its efficacy and in its ability to improve the survival rate in patients with an advanced stage. The addition of glycerol to the culture medium prior to irradiation of an oral squamous cell carcinoma cell line (Ca9-22) bearing a mutant p53 (mp53) gene was found to increase the radiosensitivity of these cells. Glycerol, when present in the culture medium, enhanced the radiation sensitivity and extent of apoptosis following X-irradiation in the Ca9-22 cells, although neither X-rays or glycerol alone increased the extent of apoptosis. These findings suggest that pre-treatment with glycerol may enhance the effectiveness of radiotherapy against oral squamous cell carcinomas bearing an mp53 gene mutation.
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