Roles of Free Radicals Produced under Hypoxic Condition on the Tumor Development and Progression

缺氧条件下产生的自由基对肿瘤发生、发展的作用

• 批准号: 15390367
• 负责人: OKADA Futoshi
• 金额: $ 4.54万
• 依托单位: YAMAGATA UNIVERSITY (2004)Hokkaido University (2003)
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 2003
• 资助国家: 日本
• 起止时间: 2003 至 2004
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-15390367/
• 关键词: ischemia-reperfusion; free radicals; carcinogenesis; tumor progression; 低酸素環境; 低酸素インキュベーター

In the present study, we aimed to verify that intrinsically produced free radicals in the ischemia-reperfusion environment are a causative factor of common cancers. For this purpose, we used several normal and pre-malignant cultured cell lines such as FPCK-1-1 (human, colonic adenoma cell), IEC 6 (rat, immortalized intestinal cell), NIH3T3 (mouse, immortalized fibroblast), Balb3T3 (mouse, immortalized fibroblast) and QR-32 (mouse, pre-malignant fibrosarcoma). We also utilized normoxic (21% O_2) and hypoxic (1% O_2) culture chambers to create an artificial environment of ischemia-reperfusion in the culture condition. By using those materials, we obtained the following results.1)A large amount of free radicals were generated in the normal or pre-malignant cultured cells after the cells were transferred to normoxic condition from hypoxic condition.2)Spontaneous tumorigenic conversion was observed in the immortalized mouse fibroblast cell lines after repeatedly cultured in normoxic and hypoxic conditions.We are now determining the gene(s) responsible for the tumorigenic conversion.

在本研究中，我们的目的是验证在缺血再灌注环境中内在产生的自由基是常见癌症的致病因素。为此，我们使用了几种正常和癌前培养细胞系，如FPCK-1-1（人，结肠腺瘤细胞）、IEC 6（大鼠，永生化肠细胞）、NIH 3 T3（小鼠，永生化成纤维细胞）、Balb 3 T3（小鼠，永生化成纤维细胞）和QR-32（小鼠，癌前纤维肉瘤）。在培养条件下，我们还利用常氧（21%O_2）和低氧（1%O_2）培养箱来创造一个人工缺血-再灌注环境。通过使用这些材料，结果表明：1）正常或癌前培养细胞在缺氧条件下培养至常氧条件下，产生大量的自由基; 2）小鼠永生化成纤维细胞在常氧和缺氧条件下反复培养后，可发生自发性致瘤性转化。导致了肿瘤的转化

项目成果

Dominant negative hypoxia-inducible factor-1 alpha reduces tumorigenicity of pancreatic cancer cells through the suppression of glucose metabolism.

显性负性缺氧诱导因子 1 α 通过抑制葡萄糖代谢来降低胰腺癌细胞的致瘤性。

• 发表时间: 2003
• 期刊: Am J Pathol 162
• 作者: Ishikawa T;Chen J
• 通讯作者: Chen J

Tazawa, H.: "Infiltration of neutrophils is required for acquisition of metastatic phenotype of benign murine fibrosarcoma cells"American Journal of Pathology. 163. 2221-2232 (2003)

Tazawa, H.：“获得良性鼠纤维肉瘤细胞的转移表型需要中性粒细胞的浸润”美国病理学杂志。

Proteomic profiling for cancer progression: Differential display analysis for the expression of intracellular proteins between regressive and progressive cancer cell lines

• DOI: 10.1002/pmic.200401132
• 发表时间: 2005-03-01
• 期刊: PROTEOMICS
• 影响因子: 3.4
• 作者: Hayashi, E;Kuramitsu, Y;Nakamura, K
• 通讯作者: Nakamura, K

Expression of AIE-75 PDZ-domain protein induces G2/M cell cycle arrest in human colorectal adenocarcinoma SW480 cells

• DOI: 10.1016/j.canlet.2004.02.005
• 发表时间: 2004-08-10
• 期刊: CANCER LETTERS
• 影响因子: 9.7
• 作者: Hirai, A;Tada, M;Moriuchi, T
• 通讯作者: Moriuchi, T

Chen, J.: "Dominant negative hypoxia-inducible factor-1 alpha reduces tumorigenicity of pancreatic cancer cells through the suppression of glucose metabolism"American Journal of Pathology. 162. 1283-1291 (2003)

Chen, J.：“显性负性缺氧诱导因子 1 α 通过抑制葡萄糖代谢来降低胰腺癌细胞的致瘤性”美国病理学杂志。