小葉桑根主成分分析及其抑制TGF-β1所誘導肝癌細胞惡化之研究

癌症，一直都是令人聞風喪膽的疾病，肝癌不論國內外，都是盛行率前幾名的癌症，又以亞洲地區最為常見，肝癌死亡率高的原因是初期時，症狀不明顯，類似感冒，不易被發現，當有嚴重症狀或疼痛出現時，通常已是癌症晚期，使得治療不易，且預後差，可說是十分難纏的疾病。發炎時細胞所分泌的生物因子，會促進癌細胞的增生、血管新生、抑制細胞凋亡等，使治療愈發困難。在醫界及學術界中，持續積極的尋找能夠對付癌症的新藥物，近年來，因紫杉醇、秋水仙鹼等，從自然界中找到，具有抗癌活性物質的研究成功，讓許多學者開始從自然界中尋找具有新作用機制或特殊化學結構，能夠治療癌症的藥物。小葉桑(Morus australis)自古以來，在亞洲地區就作為藥品使用，其含有豐富的植化素，具有抗氧化、抗發炎、抗菌等效果，在本研究中，經HPLC的分析，我們發現，小葉桑根的萃取物中，含有Oxyresveratrol及Morusin，而小葉桑根的萃取物能夠抑制TGF-β1所誘導的人類肝癌細胞HepG2 cell的發散(Scattering)，移動(Migration)，並且能抑制細胞產生Lamellipodia等偽足，小葉桑根萃取物可透過調高E-cadherin，調降Vimentin等蛋白的表現量，並透過抑制Smad2/3路徑的來抑制TGF-β1的訊息傳遞，達到抑制由TGF-β1所誘導的人類肝癌細胞HepG2 cell的移動能力的效果。

Cancers are always the life-threatening disease all around the world, hepatocellular carcinoma (HCC) is common cancer worldwide, especially in Asia. At the early stage of HCC has no clear symptom, like fever, diarrhea etc. Once the patients have severe symptoms or pain, it has been a late stage of HCC and has a poor prognosis. It is hard to cure. The cytokines of inflammatory will promote cancer cells proliferation, angiogenesis, and inhibit apoptosis. The scientists keep finding the new compound that can cure cancer. Recently, because of the success of the anti-cancer drug Paclitaxel and anti-inflammatory arthritis drug Colchicine from natural plants, the researchers start to look for new chemical compounds that have the potential to cure cancer. According to the history of pharmacy, Morus australis has been used as medicine for thousands of years in Asia. The previous study showed Morus australis has many phytochemicals and bioactivity compounds. In the present study, the crude extract from Morus australis root (MRE) was analyzed by HPLC and confirmed that it does have Oxyresveratrol and Morusin. We found that MRE inhibited TGF-β1 induced human hepatoma cell HepG2 cell scattering and migration as well as Oxyresveratrol and Morusin. In addition, MRE up-regulated E-cadherin and down-regulated Vimentin in TGF-β1- treated HepG2 cell. By western blotting analysis, it showed these results were associated with blocking Smad2/3 signal pathway.