| 摘要: | 癌症化學預防的目的是預防、停滯，或反轉致癌劑的起始作用，或使癌細胞變成癌症的過程。植物中幾種特殊的酚類化合物，已被報導指出具有抑制突變及致癌的作用。酚類化合物具有許多生物活性包括了，抑制細胞週期、細胞增生以及抑制細胞內氧化壓力，以及誘發細胞凋亡，因為這些作用使得它具有癌症化學預防的作用。而肝癌是在東方國家最常見到的一種惡性腫瘤，然而至今仍無十分有效的藥物用以治療這種疾病。在癌症的治療中，首要目標就是選擇性的使癌細胞死亡。而細胞凋亡是一種普遍且有效率的細胞自殺途徑。許多研究顯示一些由中草藥當中萃取出的抗癌藥物其具備的抗癌活性乃是藉由誘發癌細胞進行細胞凋亡所達成。希望我們的研究可以提供開發新癌症化學預防分子的一個方向。在本計劃中，第一年利用桑黃的主要成份hispolon 用來評估其抑制人類肝癌細胞 (HepG2、Hep3B 和 J5) 生長抑制的效應、探討其誘導細胞凋亡作用機制。第二年利用人類轉移能力較強之肝癌細胞Sk-hep1 評估hispolon 抑制人類肝癌細胞進行細胞侵襲、細胞移動及貼附等功能時所扮演的角色並探討其可能作用機制。第三年以內皮細胞生長因子（vascular endothelial growth factor, VEGF）誘發人類臍靜脈血管內皮細胞（human umbilical vein endothelial cells, HUVEC）的增生（proliferation），同時添加不同濃度的hispolon，以觀察其對 HUVEC 增生的影響；同時進一步觀察hispolon 對VEGF 誘發HUVEC 細胞移行（cell migration）的影響。此研究的目的是評估hispolon 抑制血管新生成作用。因此以既有之基礎瞭解hispolon 之功能，又可以擴大應用在醫藥學方面，期望 hispolon 可對癌症的治療有所幫助。
Chemoprevention of cancer aims to prevent, arrest, or reverse either the initiation phase of carcinogenesis or the progression of neoplastic cells to cancer. A large number of natural and synthetic compounds have cancer preventive properties in cell culture or animal model studies. Several specific plant phenolic compounds were reported to inhibit mutagenesis and carcinogenesis. Phenolic compounds have shown many biological properties, including inhibit the cell cycle, cell proliferation, and oxidative stress, and to induce apoptosis that may account for cancer chemoprevention. Hepatocellular carcinoma is one of the most common malignant tumors in oriental countries. However, effective drugs for treating this disease are still unavailable. In cancer treatment, the therapeutic goal is to trigger tumor-selective cell death. Apoptosis represents a universal and exquisitely efficient cellular suicide pathway. Therefore, several studies have shown that some of chemotherapeutic agents isolated from Chinese herbal extracts exert their anticancer activity by inducing cancer cells apoptosis. We hope our studies could provide a new direction to investigate new chemopreventive compounds for cancer control. In the present plan, the first year hispolon from Phellinus merrillii extracts were used to evaluate the apoptotic effect and mechanism of growth inhibition on human liver cancer cells (HepG2、Hep3B and J5). The second year, a highly metastatic human liver cancer cell line, sk-hep1, was chosen to be treated with various concentrations of hispolon to investigate its potential for inhibiting cancer cells invasion based on that tumor metastasis are accompanied with proteolytic degradation of the extracellular matrix, changes in cell-matrix adhesion, and regulated cell motility. The third year, we examined that Vascular endothelial growth factor (VEGF) induced the proliferation of HUVEC by hispolon and hispolon reduced VEGF -induced migration of HUVEC in a Transwell migration assay. The purpose of this study evaluates the inhibitory effect of hispolon on angiogenesis. It will helpful for the academic research and applied technology development. It is important for further evaluation for its application as a cancer chemopreventive agent. |
