Prevention of Skin Cancer by Scutellaria Baicalensis

中草药黄芩（黄芩）具有多种抗炎和抗癌活性。本研究的核心假设是黄芩提取物（Scutellaria baicalensis extracts， SBE）抑制紫外线b诱导的嘧啶二聚体和DNA氧化损伤，调节紫外线b激活的信号转导级联反应和炎症反应，从而抑制光致癌的发生和促进。该项目的最初目的是确定应用SBE之前或之后是否可以预防uvb诱导的皮肤癌。该项目的最初目的是确定应用SBE之前或之后是否可以预防uvb诱导的皮肤癌。SBE将局部应用于暴露于UVB的无毛小鼠。通过分析潜伏期、肿瘤发生率和多重性来评价其保护作用。第二个目的是评估SBE对光致癌发生的开始、促进和进展的影响。一个联合uvb -致癌物模型将用于剖析SBE对uvb诱导的皮肤癌的抗启动或抗促进作用。SBE将在启动剂量UVB之前局部应用于小鼠皮肤，随后是TPA促进，或在dba启动的小鼠中应用于UCB辐射之前。通过记录肿瘤消退率和恶性转换率来检验SBE对现有皮肤肿瘤的治疗效果。第三个目的是确定SBE是否在体内和体外改变了uvb诱导的与起始和促进相关的中间端点，例如DNA光产物、DNA氧化损伤、炎症反应、原癌基因表达和AP-1因子的激活。最后，我们将进一步评估SBE对uvb诱导的人体皮肤红斑和不适的保护功效。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）的分子标记将在人体皮肤活检以及长期暴露于UVB的三维重建人体皮肤中测定。本研究的成功完成，不仅有助于草药提取物作为人类皮肤癌预防和/或治疗药物的创新应用，而且还将促进BE在其他人类恶性肿瘤中的抗癌作用的研究。

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.