- 學位論文
探討迷迭香酸及其合併順鉑對胃癌細胞的抗癌效應
Investigating the Anticancer Effects of Rosmarinic Acid and Its Combination with Cisplatin on Gastric Cancer Cells
摘要
胃作為人體消化系統中的重要器官，在分解食物中的蛋白質和 細菌方面扮演著關鍵的角色。然而，由於飲食習慣 (如高鹽、高致癌物質的飲食)、幽門螺旋桿菌感染、胃息肉和胃炎等因素，導致胃癌發生的風險增加。在治療胃癌的過程中，藥物的副作用常常導致病人在其他器官上感到不適，並且生活品質下降，因此開發新的藥物以降低藥物副作用並提高病人的生活品質變得非常重要。 迷迭香酸 (Rosmarinic acid, RA) 是一種天然多酚類化合物，具有廣泛的研究和應用價值，被應用於藥物、保健品等領域。其廣泛的生物活性包括抗氧化、抗炎、抗菌和抗病毒等，這使得它成為一種具有潛在治療和保護作用的天然物質。近年來的研究表明，迷迭香酸具有抗腫瘤效果，因此本論文進一步探討迷迭香酸以及其與順鉑合併使用對胃癌細胞的抗癌效應。 根據結果發現，KATO III 和 AGS 兩種胃癌細胞株在分別單獨 處理迷迭香酸 (RA) 和順鉑時，存活率均有下降，而在合併使用這兩 種藥物後，存活率下降更加明顯。進一步的流式細胞儀分析得出， RA 和順鉑可以導致胃癌細胞停滯在 S 期，並且 subG1 期增加，而 在合併使用這兩種藥物的情況下，細胞停滯的程度更大且促使細胞 走向凋亡。在訊息傳遞方面，實驗結果顯示 RA 和順鉑可增強 p38 的磷酸化，並增加 p53 和 p21 的表現。這些結果表明，RA 和順鉑合併使用能夠增強胃癌細胞的細胞週期停滯和凋亡訊號產生，意味著 合併使用RA和順鉑能夠提升順鉑對胃癌細胞的毒殺能力。因此，我 們推測RA合併順鉑在提升胃癌治療效果方面具有潛力。
並列摘要
The stomach, as an important organ in the human digestive system, plays a crucial role in breaking down proteins and bacteria in food. However, factors such as dietary habits (high-salt or carcinogenic diet for example), Helicobacter pylori infection, gastric polyps, and gastritis increase the risk of developing stomach cancer. During the treatment of stomach cancer, the side effects of medication often lead to discomfort in other organs and a decrease in the quality of life for patients. Therefore, the development of new drugs to reduce medication side effects and improve the quality of life for patients becomes crucial. Rosmarinic acid (RA) is a natural polyphenolic compound with significant research and application value, being utilized in medicine and health supplements. It exhibits a wide range of biological activities, including antioxidant, anti-inflammatory, antibacterial, and antiviral properties, making it a potential natural substance with therapeutic and protective effects. Recent studies have indicated that rosmarinic acid possesses anti-tumor effects. Therefore, this research aims to further investigate the anticancer effects of rosmarinic acid and its combination with cisplatin on gastric cancer cells. According to the results, both KATO III and AGS gastric cancer cell lines showed decreased cell viability when treated separately with RA and cisplatin. However, the combination of these two drugs resulted in a more significant decrease in cell viability. Further analysis using flow cytometry revealed that RA and cisplatin induced cell cycle arrest at the S phase and increased the subG1 phase in gastric cancer cells. The combined treatment of these two drugs exhibited a greater degree of cell cycle arrest and promoted cell apoptosis. In terms of signaling pathways, the experimental results demonstrated that RA and cisplatin enhanced the phosphorylation of p38 and increased the expression of p53 and p21. These findings suggest that the combined use of RA and cisplatin can enhance cell cycle arrest and apoptosis signaling in gastric cancer cells, indicating that the combination can enhance the cytotoxicity of cisplatin against gastric cancer cells. Therefore, it is speculated that the combination of RA and cisplatin holds potential in improving the therapeutic efficacy of gastric cancer treatment.