2003 Fiscal Year Final Research Report Summary
Basic study to establish molecular diagnosis and gene therapy for anticancer drug-resistant cancer cells
| Project/Area Number |
13470353
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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 |
Obstetrics and gynecology
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| Research Institution | Wakayama Medical University |
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Principal Investigator |
TANAKA Tetsuji Wakayama Medical University, Medical School, Associate Professor, 医学部, 助教授 (80275255)
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| Co-Investigator(Kenkyū-buntansha) |
OTANI Naoko Wakayama Medical University, Medical School, Assistant Staff, 医学部, 助手 (80343424)
OTANI Tsutomu Wakayama Medical University, Medical School, Assistant Staff, 医学部, 助手 (90343425)
UMESAKI Naohiko Wakayama Medical University, Medical School, Professor, 医学部, 教授 (20106339)
TANAKA Kazuharu Wakayama Medical University, Medical School, Assistant Staff, 医学部, 助手
YAGI Shigetaka Wakayama Medical University, Medical School, Assistant Staff, 医学部, 助手
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| Project Period (FY) |
2001 – 2003
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| Keywords | Uterine Cancer / Ovarian Cancer / Multidrug-resistance gene / Anti-cancer drug-resistance |
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| Research Abstract |
(1)Cellular and molecular characterization of anticancer drug-resistant cancer cells : Using more than 100 anticancer drug-resistant subclones derived from human uterine and ovarian carcinomas, their drug-sensitivities were quantitatively evaluated and compared to the results of mRNA expression profiling of the resistant subclones. In this study, we have first found some relationships of death-associated protein kinase (DAPK) and anticancer-drug sensitivities of cancer cells. Demethylation of uterine cancer cells induced DAPK expression and restored their SN38-sensitivity. Demethylation of SN38-resistant cells restored SN38-sensitivity while demethylation of CDDP-resistant cells did not affect their CDDP-sensitivities.
(2)mRNA expression profiling of the drug-resistant subclones : cDNA microarray analyses revealed mRNA expression profiling of the drug-resistant subclones. Especially, c-myc mRNA expressions were significantly suppressed in many anti-cancer drug-resistant subclones.
(3)Suppression of mRNA expression may disclose candidate genes of drug-sensitivity-regulating molecules : By using siRNA procedure, we have been discovering candidate genes of drug-sensitivity-regulating molecules. Relationship of STAT3 expression and anticancer drug-sensitivity has been investigated.
(4)Basic study on gene therapy for drug-resistant cancer cells : Recently we have identified that growth-inhibitory signals of TGF-beta1 can be completely inhibited by activin A, indicating increased activin-A in endometrial adenocarcinoma indirectly enhance cell proliferation of the cancer cells. As targets for gene therapy, therefore ; we are investigating the regulatory factors that stimulate activin A production in cancer tissues.
(5)Basic study for concurrent chemoradiation : In in vitro experiments with cervical SCC cells, we have found optimal combination of anticancer drugs with radiotherapy.
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