以光學顯微術來探討Metformin對黑色素癌幹細胞的治療效用

Abstract

背景： 癌幹細胞（ Cancer Stem Cell( CSC)）是指具有自我更新( Self-renewal)以及多細胞分化( Differentiation)等幹細胞( Stem cell) 能力的癌細胞。癌幹細胞目前被認為是造成癌症轉移、復發，或者對於化學治療、放射性治療產生抗藥性的主要原因之一。很多科學家希望能夠研究出殺死癌幹細胞的方法，以降低腫瘤抗藥性及轉移。在治療癌幹細胞的研究中，發現治療糖尿病的Metformin能有效抑制癌幹細胞。黑色素癌( Melanoma)的腫瘤中包含癌幹細胞，可以建立一個平台來測試治療癌症的方法以及研究癌幹細胞的特性。 目的： 尋求光學顯像技術來直接觀測探討Metformin在活體環境下是否能對黑色素癌幹細胞有抑制生長或殺死作用。 材料與方法： 在體外實驗部分，透過立體細胞培養技術探討Metformin對黑色素癌幹細胞的影響。在動物實驗部分，則使用多光子顯微鏡系統，來評估Metformin對雄性C57BL/6-C2J小鼠耳朵上的黑色素癌腫瘤的影響。 結果： 在細胞實驗部分，和先前研究成果一樣，Metformin的濃度越高則形成的癌細胞球團數量越少。在動物實驗方面，在經過16天治療後，治療組癌幹細胞的光學信號明顯減弱。結果顯示Metformin對黑色素癌幹細胞及癌腫瘤在經過一段時間治療後，有抑制腫瘤形成及成長作用。 結論： 光學顯微系統可觀測到短期Metformin 治療在活體和體外細胞實驗中能夠抑制黑色素癌幹細胞。

Background: Cancer stem cells ( CSCs) are cancer cells referred to have some stem cell capabilities, for example, self-renewal and multi-cellular differentiation. Cancer stem cells are now considered as one of the main causes for cancer metastasis, recurrence, and resistance to chemotherapy and radiotherapy. Many scientists have been developing methods to kill cancer stem cells to reduce tumor resistance or metastasis. Metformin, drug for type 2 diabetes, inhibiting cancer stem cell growth was shown in recent cancer research. Malignant melanoma contains cancer stem cells and it can be used to establish a platform for evaluating cancer treatment methods and characterizing cancer stem cells. Purpose: To evaluate the effect of Metformin on melanoma cancer stem cells by observing in vitro 3-D cell culture and in vivo murine with optical microscopy. Materials & Methods: In vitro experiment, we explored the effect of Metformin on melanoma cancer stem cells using 3D cell culture technique. In the animal experiment, we used a multi-photon imaging microscopy system to evaluate the effect of Metformin in ear melanoma of male C57BL/6-C2J mice. Results: The in-vitro results showed that the number of cell spheres was less for a higher concentration of Metformin and the results are similar to the papers published by other groups. In the animal experiment, the preliminary results showed that the signal of cancer stem cells for the treated group is less than the control group after 16 days of treatment. Conclusion: The overall results suggested that optical microscopy can be used to observe short-term Metformin treatment inhibiting melanoma cancer stem cells both in vitro and in vivo studies.