2005 Fiscal Year Final Research Report Summary
Effect of oxidative stress and redox-regulating proteins on tumor growth and chemosensitivity
| Project/Area Number |
16590311
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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 |
Experimental pathology
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| Research Institution | The Tazuke Kofukai Medical Reserch Institute (2005)
Kyoto University (2004) |
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Principal Investigator |
UEDA Shugo The Tazuke Kofukai Medical Research Institute, Second Division, Researcher, 医学研究所第2研究部, 研究員 (80372580)
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| Co-Investigator(Kenkyū-buntansha) |
NAKAMURA Hajime Kyoto University, Graduate School of Medicine, Associate Professor, 医学研究科, 助教授 (70303914)
MATSUTANI Hiroshi Kyoto University, Institute for Virus Research, Associate Professor, ウイルス研究所, 助教授 (50252523)
YODOI Junji Kyoto University, Institute for Virus Research, Professor, ウイルス研究所, 教授 (80108993)
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| Project Period (FY) |
2004 – 2005
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| Keywords | redox / thioredoxin / tumor / anti-cancer drug / recombinant protein / tumor growth |
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| Research Abstract |
Human thioredoxin is a multifunctional redox-active protein. We investigated the effect of recombinant human thioredoxin (rhTRX) on tumor growth and chemosensitivity. rhTRX did not affect the tumor growth of human colon carcinoma cell lines, HT-29 and HCT116, under normoxia and hypoxia culture conditions in vitro. We next investigated the effect on the growth of tumor inoculated subcutaneously in nude mice. The growth of implanted HT-29 tumors was not affected by continuous subcutaneous administration of rhTRX using osmotic pump system. When mice were injected intraperitoneally with rhTRX for 3 weeks, no promoting effect on tumor growth was detected. We found that CPT-11 is an especially effective chemotherapeutic drug on HT-29 and determined the appropriate dosage and therapeutic protocol. Intraperitoneal or continuous subcutaneous injection of rhTRX did not induce resistance against chemotherapy by CPT-11. In addition, we showed that mutated rhTRX, which redox-active cysteine residues were replaced with serine (C35STRX or C32S/C35STRX), did not affect the chemosensitivity.
We are to use GMP-leveled rhTRX for treating patients with life-threatening ARDS, which can be caused by adverse effect during chemotherapy. These results demonstrated that administration of rhTRX did not promote the tumor growth nor affect chemosensitivity in the xenotransplanted model, suggesting the safety of rhTRX therapy for cancer patients.
The results were presented at the 64th annual meeting of the Japanese Cancer Association, held in Sapporo in 2005, and published in Life Sciences in 2006 (in press).
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