| 摘要: | 腫瘤細胞經常具有轉移及復發的能力，導致預後不佳。近年來，有越來越多研究指出癌幹細胞存在於惡性腫瘤中，其具有更強的增殖和自我更新能力，從而維持腫瘤的生長，並導致治療失敗率提高。因此如何鑑定和敘述癌幹細胞的特性以便於監視，乃成為治療或預防癌症的關鍵。為了建立癌幹細胞的理想模型，本研究依據細胞型態從人類前列腺癌細胞PC-3中分離出三種不同型態的細胞holocloe、paraclone及meroclone。以群落形成實驗分析，發現holoclone細胞會形成較多聚集生長的細胞群落。在細胞球體形成實驗中，發現holoclone細胞會形成較大且數目較多的細胞球體，顯示holoclone細胞可能具有較強的自我更新能力。並使用不同藥物測試，發現holoclone細胞對於藥物α-solanine及doxorubicin具有較高的抗藥性。這些結果顯示holoclone細胞可能具有癌幹細胞的特性，具有自我更新和抗藥性能力。PC-3細胞形成的懸浮球體細胞大量表現癌幹細胞標誌基因，包括Naong、Sox-2、OCT-4與c-Myc。PC-3懸浮球體衍生細胞亦對solasodine與4-OOH CPA等藥物具有抗藥性。我們也發現α-solanine可劑量依賴性抑制球體細胞形成。總結以上結果，本研究所分離出的PC-3 holoclone細胞與懸浮球體細胞，其具有自我更新能力及抗藥性，並且表現癌幹細胞標誌基因。在未來此細胞模型可應用於研究癌症幹細胞的特性與治療藥物的開發。
Tumor cells usually exhibit metastatic and recurrence properties, and result in poor prognosis. In recent years, more studies indicate that cancer stem cells, present in malignant tumors, possess greater proliferative and self-renewal capacities. Cancer stem cells are associated with tumor recurrence and inefficient treatment. Therefore, identification and description of the properties of cancer stem cells are important for monitoring cancer progression, and the treatment or prevention of cancer. In order to establish the model for cancer stem cells study, we isolated three types of cell, holocloe, paraclone and meroclone from human prostate cancer cells PC-3 by cell morphology in the present study. In colony formation assay, we found holoclone cells growth with close cell-cell contact morphology. In spheroid formation assay, holoclone cells formed many large spheroids, which suggesting holoclone cells may possess strong self-renewal capacity. Holoclone cells also present drug-resistant characteristics against α-solanine and doxorubicin. These results demonstrated that holoclone PC-3 cells may possess cancer stem cells properties, including self-renewal capacity and drug-resistance. In addition, PC-3 cells formed spheroids highly express cancer stem cell marker genes, such as Naong, Sox-2, OCT-4 and c-Myc. Spheroid-derived PC-3 cells are more resistant to solasodine and 4-OOH CPA compared with parental PC-3 cells. Interestingly, it is found that α-solanine inhibited PC-3 cells spheroids formation with a dose-dependent manner. Taken together, PC-3 holoclone cells and spheroids exhibit cancer stem cells characteristics, such as self-renewal, drug-resistant potentials, and expressing cancer stem cells marker genes. The cell model can be used to study the properties of cancer stem cells and development of therapeutic drugs in the future. |
