Anti-tumor mechanism of a dietary and herbal mixture

描述（由申请人提供） 最近，在两项小规模的1/11期临床试验中，一种“精选蔬菜和草药混合物（SV）”显示出与对照组相比，晚期非小细胞肺癌（NSCLC）患者的中位生存时间（MST）延长了3倍。在BALB/c小鼠中使用L1肺腺癌模型的初始实验室动物研究表明，SV的两种活性成分的组合能够抑制高达80%的肿瘤生长。SV由全植物提取物的混合物组成，这些植物提取物完全来自天然的、常见的蔬菜和长期用于草药的植物。SV的成分是根据其已知的抗病毒、抗肿瘤和免疫增强活性来选择的。该假说认为，这些活性分子的生物化学和生物学效应相结合，能够赋予一个增强的免疫和肿瘤抑制活性。本研究的目的是比较SV及其水或甲醇提取物（SVE）的抗肿瘤效果，并阐明其抗肿瘤作用的细胞和分子机制。具体目标是：1）检查SV及其提取物的抗肿瘤功效; 2）研究SV及其提取物在细胞水平和各种组织病理学性质上对肿瘤发展的影响;和3）检查SV及其提取物对调节正常和肿瘤细胞的生长和凋亡的分子信号传导途径的影响。本研究拟利用L1-BALB/c小鼠肿瘤模型，探讨SV及其提取物对肿瘤细胞生长、凋亡、转移和血管生成的影响，并初步探讨SV抗肿瘤作用的分子基础。将在对照和SV处理的小鼠中检查调节正常和肿瘤细胞的生长和凋亡的各种信号传导途径和分子。SV是一种安全、无毒的饮食混合物，可与其他癌症治疗方案同时服用。本研究将为优化SV的制备和制剂提供信息，并确定其最显著的抗肿瘤活性，从而为进一步开发或改进抗肿瘤药物提供潜在靶点。该结果也可能导致SV制剂质量控制的体外测定的发展。作为一种抗癌食品补充剂，尽管迄今为止SV的疗效主要在NSCLC患者中显示，但基于其设计的抗肿瘤和免疫增强活性，预计SV应具有广谱的抗肿瘤疗效

DESCRIPTION (provided by applicant) Recently a "Selected Vegetable and Herbal Mix (SV)" was shown to prolong the median survival time (MST) of advanced non-small cell lung cancer (NSCLC) patients 3-fold compared to controls in two small scale phase 1/11clinical trials. Initial laboratory animal study using the L1 lung adenocarcinoma model in BALB/c mice showed that combination of two of the active ingredients of SV was able to inhibit up to 80% of the tumor growth. The SV consists of a mixture of whole plants extracts solely from natural, commonly available vegetables and plants that have long been used in herbal medicine. The ingredients of SV were selected for their known anti-viral, anti-tumor and immune enhancing activities. The hypothesis is that the combined biochemical and biological effects of those active molecules are able to endow one with enhanced immune and tumor suppressive activities. The objectives of this proposal are to compare the anti-tumor efficacy of SV and its water or methanol extracts (SVE) and to elucidate the cellular and molecular mechanism for their anti-tumor effect. The specific aims are: 1) to examine the anti-tumor efficacy of SV and its extracts; 2) to investigate the effect of SV and its extracts on tumor development at cellular level and in various histopathological properties and 3) to examine the effect of SV and its extracts on molecular signaling pathways regulating growth and apoptosis of normal and tumor cells. The L1-BALB/c model will be used to explore the effect of SV and its extracts on tumor cell growth, apoptosis, metastasis and angiogenesis, as well as to identify molecular basis for the anti-tumor effect of SV. Various signaling pathways and molecules regulating the growth and apoptosis of normal and tumor cells will be examined in control and SV treated mice. SV is a safe, non-toxic dietary mixture that can be taken concurrently with other cancer therapeutic regimens. This study shall provide information for optimizing the preparation and formulation of SV and to identify its most significant anti-tumor activities that could reveal potential targets for further development or improvement of anti-tumor agents. The results could also lead to the development of in vitro assays for quality control of the SV preparation. As an anti-cancer food supplement, although the efficacy of SV has so far been shown mainly in the NSCLC patients, based upon its designed anti-tumor and immune enhancing activities, it is anticipated that SV should have a wide spectrum of anti-tumor efficacy