大腸癌細胞中rTSβ蛋白的表現與5-FU抗藥性之研究

大腸癌是台灣地區最普遍的惡性腫瘤，也是位在肝癌及肺癌之後，癌症致死率排名第三位的惡性腫瘤。大腸癌的治療以手術為主，並配合化學治療及放射治療。而在化學治療中，5-fluorouracil (5-FU)是使用最廣泛的藥物。但是隨著抗藥性的產生，使得5-FU臨床上的應用受到限制。因此，本文的目的為研究人類大腸癌細胞中rTSβ蛋白的表現，以了解是否rTSβ蛋白可以作為5-FU抗藥性之標記。我們由澄清綜合醫院的組織銀行(tissue bank)中，收集21位病患的大腸癌檢體來進行研究；並且利用細胞毒性分析法來檢測5-FU及5-FU加上Leucovorin對人類大腸癌細胞株 (H630及H630-1)的毒殺作用。首先利用西方墨點法及免疫細胞染色法來測量rTSβ蛋白的表現。結果發現，同一病患中，如果大腸癌細胞中有rTSβ蛋白的表現 (13/21)，其表現量明顯高於腫瘤周圍正常細胞中rTSβ蛋白的表現量。而具有rTSβ蛋白表現的大腸癌細胞株 H630-1，其對於5-FU的IC50也較無rTSβ蛋白表現的H630高；如果再加入Leucovorin的話，則會降低對5-FU的IC50。換句話說，具有rTSβ蛋白表現的細胞也對5-FU具有較高的抗藥性，而Leucovorin則可以增強5-FU對細胞的毒殺作用。因此，本研究希望藉由這種rTS β蛋白與5-FU抗藥性的關係，來確立rTSβ蛋白為一種大腸癌新的5-FU抗藥基因，並以此結果來改善5-FU在臨床上的治療成效。更進一步希望藉由rTSβ蛋白的表現，來作為大腸癌病患預後的指標。

Colorectal cancer is the most common malignancy in Taiwan and the third leadingcause of death of cancer, following hepatic cancer and lung cancer. Main treatment of colorectal cancer is surgical intervention and/or chemotherapy and radiotherapy, if necessary. For chemotherapy, 5-FU is the most commonly used anti-cancer drug. Nonetheless, elevation of drug resistance restricts the broad application of 5-FU. In this study, we therefore measured expression of rTSβin human colon cancer as a novel 5-fluroracil resistance marker. We collected 21 pairs of colon cancer biopsies from tissue bank of Chen Ching General hospital. In vitro, we further measured cytotoxicity of 5-FU and 5-FU plus Leucovorin in H630 and H630-1 colon cancer cell lines. In vitro, H630-1 (with rTSβoverexpression) had obviously higher IC50 of 5-FU than that of H630. IC50 of 5-FU decreased when Leucovorin was added. In conclusion, our results show a close association between rTSβexpression and drug resistance to 5-FU in the human colorectal cancer. These results further suggest that rTSβexpression could be a novel 5-FU resistance marker of colorectal cancer.