曾淑玲王馨誼Xin-Yi Wang醫學研究所2026-10-299999-12-312019https://handle.ncl.edu.tw/11296/952d9phttps://scholars.csmu.edu.tw/handle/123456789/36457過去Otto Warburg發現癌細胞具有較高的葡萄糖代謝速率，因此提出瓦氏效應(Warburg effect)的假說，然而根據瓦氏效應的理論，葡萄糖最終會代謝生成乳酸，近期的研究發現乳酸能促進癌細胞侵襲及轉移的能力，或是可作為癌細胞的能量來源，且甚至能增加癌幹細胞的活性，但目前對於乳酸對大腸直腸癌細胞的影響仍尚不清楚，因此本研究想進一步了解乳酸對大腸直腸癌細胞株SW480和SW620細胞增生及對其糖解作用和癌幹細胞活性的影響。本研究將大腸直腸癌細胞株SW480和SW620經高濃度葡萄糖及低濃度葡萄糖馴化後進行試驗。首先我們利用MTT試驗觀察乳酸對於癌細胞增生的影響，將細胞處理不同的乳酸濃度，發現乳酸能促進SW480細胞增生，但對SW620細胞則無明顯的影響；以海馬能量測定儀測定糖解活性，發現乳酸會降低SW480細胞的糖解效率，尤其對SW480L細胞的影響最為明顯；最後透過Sphere formation assay對SW480細胞處理不同乳酸濃度，觀察乳酸對SW480細胞癌幹細胞活性的影響，發現乳酸能促進SW480細胞球狀細胞的生成。總結以上結果，發現乳酸可以促進大腸直腸癌細胞增生，改變細胞糖解作用的效率，甚至可以進一步促進癌幹細胞的生成，然而其詳細的調控機轉及透過的路徑仍有待日後進一步確認與釐清。Cancer cells have the tendency to increase uptake of glucose, a phenomenon defined as the “Warburg effect” which was discovered by Otto Warburg in 19th century. Evidence indicates that lactate promotes invasion and metastasis, is a fuel for TCA cycle, and even enhance cancer stem cell activity in cancer cells. However, the effect of lactate in colorectal cancer cells remains unclear. The aim of this study was to determine the effect of lactate altered proliferation and cancer stem cell activity in human colorectal cancer cell lines SW480 and SW620.In order to determine whether lactate can effect colorectal cancer cells proliferation, we treated cells with different concentration of sodium L-lactate and cell proliferation was assessed by MTT assay. We observed that lactate enhanced SW480 cells proliferation, but SW620 cells didn’t. Next, the analysis by seahorse XFe24 analyzer showed that lactate could decrease the glycolytic activity in SW480 cells. Finaly, in order to determine whether lactate can increase the cancer stem cell activity of colorectal cancer cells, we treated cells with different concentration of sodium L-lactate by sphere formation assay. Our results indicated that lactate enhanced spheres growth in SW480 cells.Based on the above results, lactate had a certain influence on proliferation, glycolytic activity and cancer stem cell activity in colorectal cancer cells. In this study, we only show the effect of lactate in colorectal cancer cells. However, the mechanism remains unknown and should be further evaluated.大腸直腸癌瓦氏效應乳酸糖解作用癌幹細胞colorectal cancerwarburg effectlactateglycolysiscancer stem cellsthesis