Betaine 抑制人類骨肉瘤細胞侵襲轉移之機制探討

根據全球癌症統計資料，骨肉瘤病人患有轉移性疾病或復發患者的預後仍然非常差，骨肉瘤有很高的轉移能力會轉移至遠端的器官組織，肺部為最常見的轉移部位是導致骨肉瘤死亡的主要原因。甜菜鹼(Betaine)是一種天然化合物，為穩定及天然無害的成分，甜菜鹼具有促進健康的特性，被廣泛運用在許多地方，像是:氧化還原特性、肝臟疾病、慢性腎臟病、心血管疾病、神經保護等等，但在癌症研究上，甜菜鹼跟癌症的相關研究尚未清楚。Epithelial mesenchymal transition (EMT)又稱為上皮細胞間質轉化，被認為是許多癌症的腫瘤遷移和侵襲的過程。本研究希望探討Betaine是否可抑制骨肉瘤癌細胞U2OS、143B的侵襲能力及Betaine對於EMT相關機制的影響。在細胞實驗中，利用MTT assay分析Betaine對骨肉瘤細胞的存活率，Zymography來分析u-PA及MMPs酵素的活性，Wound healing 分析細胞爬行的影響，Boyden chamber分析細胞侵襲以及移動的能力影響及Western Blotting分析蛋白質表現量，發現U2OS和143B腫瘤細胞經不同濃度的甜菜鹼處理與控制組相比發現PI3K蛋白表現量有減少，因此猜測甜菜鹼調控之轉移與PI3K pathway有關。本研究結果發現Betaine濃度在100 ?M對骨肉瘤細胞沒有顯著毒殺效果，Betaine可能有抑制骨肉瘤細胞侵襲及移動能力。

According to global cancer statistics, the prognosis of osteosarcoma patients with metastatic disease or recurrence is still very poor. Osteosarcoma has a high ability to metastasize to distant organs and tissues, and the lungs are the most common site of metastasis, leading to Osteosarcoma is the leading cause of death. Betaine is a natural compound. It is a stable and natural harmless ingredient. Betaine has health-promoting properties and is widely used in many places, such as: redox properties, liver disease, chronic kidney disease, heart disease, etc. Vascular diseases, neuroprotective properties, etc. However, in cancer research, the research related to betaine and cancer is not yet clear. Epithelial mesenchymal transition (EMT), also known as epithelial mesenchymal transition, is considered to be the process of tumor migration and invasion in many cancers. This study hopes to explore whether Betaine can inhibit the invasion ability of osteosarcoma cancer cells U2OS and 143B and the impact of Betaine on EMT-related mechanisms. In cell experiments, MTT assay was used to analyze the cell viability by Betaine treatment on osteosarcoma cells, Zymography was used to analyze the activity of u-PA and MMPs enzymes, Wound healing was used to analyze the impact of cell migration, Boyden chamber was used to analyze the impact of cell invasion and motility capabilities 、 Western Blotting analysis of protein expression showed that U2OS and 143B tumor cells were treated with different concentrations of betaine and found that PI3K protein expression was reduced compared with the control group. Therefore, it is speculated that the transfer of betaine regulation is related to the PI3K pathway. The results of this study found that Betaine at a concentration of 100 ?M has no significant cytotoxity on osteosarcoma cells. Betaine may have the ability to inhibit the invasion and migration of osteosarcoma cells.