Identification of tumor promoter of UV-carcinogenesis of the skin and the suppression of carcinogenesis by inhibiting tumor promoter

皮肤紫外线致癌的肿瘤启动子的鉴定以及通过抑制肿瘤启动子抑制癌变

• 批准号: 14570807
• 负责人: UEDA Masato
• 金额: $ 1.79万
• 依托单位: Kobe University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2002
• 资助国家: 日本
• 起止时间: 2002 至 2003
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-14570807/
• 关键词: UV-carcinogenesis; tumor promotor; cyclooxygenasa-2; free radical; EGF-receptor; oxidized diacylglycerol; telomerase; apoptosis; ゲニステイン

(1)Cyclooxygenase-2 (COX-2) has been shown to be activated by UV and has been suggested to act as a tumor promotor. We examined the mechanism of COX-2 activation by UVB in HaCaT keratinocytes and found that oxygen radicals and activation of EGF-receptor are involved in this event. (2)To reveal that oxidized diacylglycerol acts as tumor promotor of UV-carcinogenesis, oxidized diacylglycerol was applied to the mouse skin after the initiation with DMBA. However, we could not observe the tumor formation. (3)Telomerase activation is the critical step for carcinogenesis and the inhibition of telomerase may lead to suppression of carcinogenesis. The mechanism of telomerase activation in squamous cell carcinome cells was examined and we found that the EGF-receptor activity is important for the telomerase activity. (3)Induction of apoptosis is crucial for the treatment of cancer. Genistein, an isoflavon in soy beans, was examined whether it augments apoptosis in melanoma cells by cisplatinum. Treatment with genistein and cisplatinum increased apoptosis in association with the decreased expression of bcl-2 and bcl-xL and increased expression of Apaf-1.

(1)环氧合酶-2(COX-2)被发现可被紫外线激活，并被认为是一种肿瘤促进剂。我们研究了UVB激活HaCaT角质形成细胞COX-2的机制，发现氧自由基和EGF受体的激活参与了这一事件。(2)为了揭示氧化二甘油在紫外线致癌中的促癌作用，在DMBA引发下，将氧化二甘油应用于小鼠皮肤。但未能观察到肿瘤的形成。(3)端粒酶激活是癌变的关键步骤，抑制端粒酶活性可能导致抑制癌变。研究了鳞癌细胞中端粒酶的激活机制，发现EGF受体活性对端粒酶活性有重要影响。(3)诱导细胞凋亡是肿瘤治疗的关键。金雀异黄素是大豆中的一种异黄酮，研究了它是否通过顺铂促进黑色素瘤细胞的凋亡。金雀异黄素和顺铂治疗后细胞凋亡率增加，同时bcl2和bclxl表达降低，APAF-1表达增加。

项目成果

Budiyanto A, Bito T, Kunisada M, Ashida M, Ichihashi M, Ueda M: "Inhibition of the EGF receptor suppresses telomerase activity in HSC-1 human cutaneous squamous cell carcinoma cells."J Invest Dermatol. 121. 1088-1094 (2003)

Budiyanto A、Bito T、Kunisada M、Ashida M、Ichihashi M、Ueda M：“抑制 EGF 受体可抑制 HSC-1 人皮肤鳞状细胞癌细胞中的端粒酶活性。”J Invest Dermatol。

Budiyanto A, et al.: "Inhibition of the epidermal growth factor receptor suppresses telomerase activity in HSC-1 human cutaneous squamous cell carcinoma cells"J investigative Dermatology. 121. 1088-1094 (2003)

Budiyanto A 等人：“抑制表皮生长因子受体可抑制 HSC-1 人皮肤鳞状细胞癌细胞中的端粒酶活性”J Investigative Dermatology。

Tamura S, Bito T, Ichihashi M, Ueda M: "Genestein enhances the cisplatin-induced inhibition of cell growth and apoptosis in human malignant melanoma cells."Pig Cell Res. 16. 470-476 (2003)

Tamura S、Bito T、Ichihashi M、Ueda M：“Genestein 增强了顺铂诱导的人类恶性黑色素瘤细胞生长和细胞凋亡的抑制作用。”Pig Cell Res。

Tamura S, et al.: "Genistein enhances the cisplatin-induced inhibition of cell growth and apoptosis in human malignant melanoma cells"Pigment Cell Research. 16. 470-476 (2003)

Tamura S 等人：“金雀异黄素增强顺铂诱导的人类恶性黑色素瘤细胞生长和凋亡的抑制”色素细胞研究。

Ashida M, et al.: "Involvement of EGF receptor activation in the induction of cyclooxygenase-2 in HaCaT keratinocytes after UVB"Experimental Dermatology. 12. 445-452 (2003)

Ashida M 等人：“UVB 后 HaCaT 角质形成细胞中 EGF 受体激活参与环氧合酶 2 的诱导”实验皮肤病学。