Prevention of Skin Cancer by Scutellaria Baicalensis

中草药黄芩具有多种抗炎、抗癌活性。该建议的中心假设是，黄芩提取物（SBE）抑制紫外线（UV）B诱导的嘧啶二聚体和氧化DNA损伤，并调节UVB激活的信号转导级联和炎症反应，从而抑制光致癌的启动和促进。该项目的最初目的是确定SBE应用前或应用后是否能防止UVB诱导的皮肤致癌作用。该项目的最初目的是确定SBE应用前或应用后是否能防止UVB诱导的皮肤致癌作用。在暴露于UVB期间，将SBE局部应用于无毛小鼠。将通过分析潜伏期、肿瘤发生率和多重性来评价保护作用。第二个目的是评估SBE对光致癌作用的启动、促进和进展的影响。将使用UVB-致癌物组合模型来剖析SBE对UBV诱导的皮肤致癌作用的抗引发或抗促进作用。在开始剂量的UVB之前，将SBE局部应用于小鼠皮肤，然后进行TPA促进，或者在DMBA启动的小鼠中在UCB辐射之前应用。将通过记录肿瘤消退率和恶变率来测试SBE对现有皮肤肿瘤的治疗效果。第三个目的是确定SBE是否改变UVB诱导的与启动和促进相关的中间终点，例如DNA光产物、氧化DNA损伤、炎症反应、原癌基因表达和AP-1因子在体内和体外的活化。最后，我们将进一步评估SBE在保护UVB引起的人体皮肤红斑和不适方面的功效。DNA损伤（嘧啶二聚体和8-OHdG）、细胞凋亡（p53蛋白表达）和细胞增殖（PCNA）的分子标志物将在人皮肤活检以及长期暴露于UVB的三维重建人皮肤中测定。这些研究的成功完成不仅将有助于创新地使用草药提取物作为预防和/或治疗人类皮肤癌的药物，而且还将促进BE在其他人类恶性肿瘤中抗癌作用的研究。

Chinese herbal medicine Huang Qin (Scutellaria baicalensis) has a variety of anti-inflammatory and anti-cancer activities. The central hypothesis of this proposal is that Scutellaria baicalensis extracts (SBE) inhibit ultraviolet (UV) B-induced pyrimidine dimers and oxidative DNA damage, and modulate UVB-activated signal transduction cascades and inflammatory responses, thereby suppressing the initiation and promotion of photocarcinogenesis. The initial aim of the project is to determine if pre- or post-application of SBE prevents UVB-induced skin carcinogenesis. The initial aim of the project is to determine if pre- or post-application of SBE prevents UVB-induced skin carcinogenesis. SBE will be topically applied to hairless mice during exposure to UVB. The protective effect will be evaluated by analyzing the latency period, tumor incidence and multiplicity. The second aim is to evaluated the effects of SBE on the initiation, promotion, and progression of photocarcinogenesis. A combined UVB-carcinogen model will be used to dissect the anti-initiational or anti-promotional effects of SBE on UBV- induced skin carcinogenesis. SBE will be topically applied to mouse skin before an initiating dose of UVB, followed by TPA promotion, or applied before UCB radiation in DMBA-initiated mice. The therapeutic effect of SBE will be tested on the existing cutaneous tumors by recording the tumor regression rate and malignant conversion rate. The third aim is to determine if SBE modifies UVB-induced intermediate endpoints relevant to initiation and promotion, e.g. DNA photoproducts, oxidative DNA damage, inflammatory responses, protooncogene expression and activation of AP-1 factor in vivo and in vitro. Lastly, we will further evaluate the efficacy of SBE in protection of UVB-induced erythema and discomfort in human skin. The molecular markers of DNA damage (pyrimidine dimers and 8-OHdG), apoptosis (p53 protein expression), and cell proliferation (PCNA) will be determined in the human skin biopsies as well as in 3-dimensional reconstituted human skin chronically exposed to UVB. Successful completion of the proposed studies will not only contribute to innovative use of herbal extracts as preventive and/or therapeutic agents against human skin cancer, but also promote the research on the anti-cancer action of BE in other human malignancies.