在動物體內研究丹參酮ⅡA與5-FU對大腸癌的協同作用與分子機制

惡性腫瘤是台灣十大死亡原因的首位。結腸直腸癌居惡性腫瘤死亡原因的第三位。丹參酮ⅡA是丹參(danshen)的提取物，我們先前研究證實，在體外，丹参酮ⅡA有抑制人類大腸癌細胞colo 205 的增殖和引起凋亡的功效，也可以減少colo 205細胞侵襲和轉移能力。但在動物體內，單獨使用丹參酮ⅡA對colo 205細胞異種皮移殖腫瘤卻沒有抑制的功效。所以本研究將研究丹參酮ⅡA和西藥的交互作用，利用動物實驗探討丹參酮ⅡA合併抗大腸癌的化療藥物5-FU的作用。將免疫不全小鼠(NOD.CB17-Prkdc-scid/JTcu mice)皮下接種人類大腸癌細胞colo 205 2×106 /0.2 ml，等到大腸癌細胞移植成功後，才開始分別以腹腔注射給予5-Fu (I.P)、灌胃口服給予丹參酮IIA (P.O) 或丹參酮ⅡA合併5-FU（20 mg/ 每公斤體重/ 0.2 ml/ 每劑）進行治療，之後觀察及測量每組免疫不全小鼠體重及腫瘤生長情形，治療30日後犧牲，犧牲前秤體重，犧牲後取瘤秤重，檢測丹參酮ⅡA合併5-FU對colo 205細胞異種皮移殖腫瘤的治療效應。並分別利用西方墨點法和蛋白質體學的方法評估單用丹參酮ⅡA，西藥5-FU與中西合併用藥對於組織蛋白質的差異，探討可能的分子機轉，對日後臨床價值，可提供有效的參考資料。
關鍵字：丹參酮ⅡA，5-FU，大腸癌，協同作用，動物體內

The synergistic effects and molecular mechanisms for colon cancer were treated with Tanshinone IIA and 5-FU in vivo

Malignant tumor is in the first leading causes of death in Taiwan. Colon cancer is the third leading cause of cancer-related death in Taiwan.. Tanshinone II is one of the compositions of danshen (Salvia miltiorrhiza, Bunge). Our previous studies showed that Tan-IIA could inhibit the proliferation and induce apoptosis, Tan-IIA also could inhibit invasion and metastasis in human colon cancer colo 205 cells in vitro. But the efficacy for colo 205 cells xerograft tumors in SCID mice were treated with Tan-IIA was not significant in vivo. In the present study we investigated the antitumor activity of Tanshinone II A with 5-FU in human colon cancer xenograft model. For in vivo studies, male SCID mice (3 weeks old, number＝24) were xenografted with colo 205 cells tumors (3×106 /0.2 ml ) and on day 10 onwards 5-FU (20 mg/kg ,I.P, Q.W1 ) +corn oil (0.2ml ,P.O,Q.W3.5 ); 5-FU (20 mg/kg ,I.P, Q.W1 ) +Tan IIA (20 mg/kg ,P.O,Q.W3.5 ); were administered for 30 days. As a control, xenografted tumors were separately treated with normal saline (0.2ml ,I.P, Q.W1 ) +corn oil (0.2ml ,P.O,Q.W3.5 );. The xenografted tumor volumes and animal body weight were measured every three days.
關鍵字：Tanshinone IIA，5-FU，colon cancer，synergistic efficacy，in viv