Anti-tumor mechanism of a dietary and herbal mixture

描述(由申请人提供) 最近，在两个小规模的1/11期临床试验中，一种“精选蔬菜和草药混合物(SV)”被证明可以将晚期非小细胞肺癌(NSCLC)患者的中位生存时间(MST)延长3倍。使用BALB/c小鼠L1肺腺癌模型进行的初步实验动物研究表明，SV的两种有效成分的组合能够抑制高达80%的肿瘤生长。SV由完全从天然、常见的蔬菜和长期用于草药的植物中提取的整个植物的混合物组成。根据已知的抗病毒、抗肿瘤和免疫增强活性，选择了SV的成分。假说是，这些活性分子的生物化学和生物效应相结合，能够赋予它们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)的抗肿瘤作用，并阐明其抗肿瘤的细胞和分子机制。其具体目的是：1)检测SV及其提取物的抗肿瘤作用；2)从细胞水平和多种组织病理学的角度研究SV及其提取物对肿瘤发生的影响；3)研究SV及其提取物对调节正常细胞和肿瘤细胞生长和凋亡的分子信号通路的影响。本实验将利用L1-BALB/c小鼠模型，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，并探讨SV抗肿瘤作用的分子基础。在对照组和SV处理的小鼠中，将检测调节正常和肿瘤细胞生长和凋亡的各种信号通路和分子。SV是一种安全、无毒的饮食混合物，可以与其他癌症治疗方案同时服用。本研究将为优化SV的制备和处方提供信息，并确定其最重要的抗肿瘤活性，以揭示进一步开发或改进抗肿瘤药物的潜在靶点。这一结果也可能导致体外检测方法的发展，用于SV制剂的质量控制。作为一种抗癌食品补充剂，尽管到目前为止，SV的疗效主要表现在非小细胞肺癌患者身上，但基于其设计的抗肿瘤和免疫增强活性，预计SV应具有广泛的抗肿瘤功效

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