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）已被证明可被紫外线激活，并被认为是肿瘤的促进剂。我们研究了UVB在HaCaT角质形成细胞中激活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)为了揭示氧化二酰基甘油在紫外线致癌作用中的肿瘤促进作用，我们将氧化二酰基甘油经DMBA诱导后涂于小鼠皮肤。但未观察到肿瘤的形成。(3)端粒酶活化是癌变的关键步骤，抑制端粒酶可抑制癌变。研究了端粒酶在鳞状细胞癌细胞中的活化机制，发现egf受体活性对端粒酶活性起重要作用。(3)诱导细胞凋亡对肿瘤的治疗至关重要。染料木黄酮，大豆中的异黄酮，通过顺铂检测其是否增加黑色素瘤细胞的凋亡。染料木素和顺铂治疗增加细胞凋亡，降低bcl-2和bcl-xL的表达，增加Apaf-1的表达。

(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.