探討中國橄欖萃取物於不同培養條件下造成大腸癌細胞生長及集體遷移狀態的影響

Abstract

根據衛生福利部民國110年癌症登記報告，大腸癌在台灣的發病率位居第二，死亡率則排名第三。當大腸癌轉移到其他器官時，患者的五年生存率急劇下降。研究指出，某些癌細胞在遷移過程中不會完全經歷上皮-間質轉化 （EMT），而是同時保留部分上皮和間質特徵，以集體遷移為主要方式遷移方式。集體遷移雖需要更多能量，但也增強了癌細胞的轉移能力。中國橄欖萃取物（COE）已知能干擾癌細胞能量代謝並抑制其生長。本研究旨在探討COE是否通過影響集體遷移來抑制癌細胞的遷移能力。結果顯示，COE在一般細胞培養環境下能有效抑制癌細胞的生長和遷移，而對EMT相關蛋白的表現無顯著影響。但其影響E-cadherin在細胞內的分佈，可能從而改變遷移邊緣細胞的形態。此外，在不同環境條件下實驗結果顯示，環境中的丙酮酸含量會影響COE對癌細胞生存率的抑制效果，而環境中的血清濃度則影響其對癌細胞遷移的抑制。這一差異可能源於細胞生存與遷移所需能量規模的不同。然而，透過本研究結果顯示環境中丙酮酸的含量（pyruvate）雖對COE引起的遷移邊緣細胞形態變化有影響，但並不改變COE抑制癌細胞遷移的效果。總結來看，在本研究模型中，COE 本身所造成的能量缺乏已足以抑制癌細胞遷移，丙酮酸所造成的能量變化無法干擾此一現象，但遷移邊緣細胞形態變化是否為COE抑制癌細胞遷移的重要因子仍需更進一步確認。

According to the 2021 Cancer Registry Annual Report by Taiwan's Ministry of Health and Welfare, colorectal cancer ranks second in incidence and third in mortality among all cancers in Taiwan. When colorectal cancer metastasizes to other organs, the five-year survival rate of patients markedly declines. Studies indicate that some type of cancer cells do not fully undergo epithelial-to-mesenchymal transition （EMT） during migration, but retain both epithelial and mesenchymal characteristics, primarily migrating in clusters. Although collective migration requires more energy, it also enhances the metastatic capability of cancer cells. Chinese olive extract （COE） is known to interfere with cancer cell energy metabolism and inhibit their growth. This study aims to explored whether COE inhibits cancer cell migration by affecting collective migration. The results showed that COE effectively inhibited cancer cell survival growth and migration in normal cell culture conditions without significantly affecting the expression of EMT-related proteins. However, it influences the distribution of E-cadherin within cells, potentially altering the morphology of cells at the migration edge. Additionally, the experimental results under different environmental conditions revealed that the pyruvate content in the environment affected COE's ability to inhibit cancer cell survival, while serum concentration influenced its ability to inhibit cancer cell migration. This difference may be due to the varying energy demands required for cell survival and migration. Nevertheless, the study results show that although the environmental pyruvate content affects COE-induced morphological changes of cells at the migration edge, it did not alter COE's inhibitory effect on cancer cell migration. In conclusion, in this study model, the energy deficiency caused by COE alone is sufficient to inhibit cancer cell migration, and the energy changes induced by pyruvate cannot disrupt this phenomenon. However, further investigation is needed to confirm whether the morphological changes in migration edge cells are a key factor in COE’s inhibition of cancer cell migration.