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

(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。

(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.