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成樂其,金聖勳,李權益 대한동의병리학회 1996 동의생리병리학회지 Vol.10 No.2
“怪病必瘀 久病必瘀”라 하여 癌 등의 難治病에는 瘀血證이 자주 나타나, 直接的인 抗腫류作用외에도 惡性腫瘍으로 인한 疑血과 織溶系統을 調節하는 作用이 있는 活血化瘀法은 현재 임상세선 活用 價値가 높다. 이에 本 論文에서는 活血祛瘀劑 및 安神劑로 活用되고 있는 丹蔘을 이용 抗癌 및 抗轉移 效果를 糾明하고 活性 物質을 採索함으로써 癌 治療에 도움이 되고자 한다. in vitro에서 B16-Fo와 A549 癌細胞 등의 패癌株에 對한 細胞毒性, 複合細胞外基質과 單味細胞外基質에 對한 細胞附着 沮止作用, 血小板疑集 促進劑중의 하나인 ADP에 對한 血小板凝集抑制作用, 有效 分劃으로부터 分離된 有效物質의 構造同定, 多樣한 사람 癌株에 對한 ED(50)값 및 自然殺害作用을 檢討하고, in vivo에서는 丹蔘의 有效 分劃을 S-180이 移植된 ICR 생쥐에 經口 投與한 後, 體重變化와 T/C%를 尾靜脈에 B16-Fo를 注入 후 C157BL/6의 pulmonary colonization assay, 臟器무게, WBC 및 platelet 數 等을 測定하였다. 丹蔘 分劃중 ethly ether층이 抗癌 및 抗轉移效果에 있어 가장 有意性있는 效果가 認定되었고, 이 층에서 分離된 tanshione IIA는 丹蔘의 主要 抗癌活性物質로 이를 이용한 數種 癌株의 細胞毒性 實驗에서 ED(50)이 모두 1.5㎍/㎖ 以下로 나타나 有效한 抗腫瘍 效果을 보였으며, 10㎍/㎖부터 HL-60에 대해 DNA fragmentation을 나타냈다. In order to confirm the antitumor effect of Salviae miltiorrhizae Radix(SMR) and isolate its active compound, the experiment was done. In vitro cytotoxicity against several cancer cell lines, inhibition of cell adhesion to extracellular matrix, inhibition of platelet aggregation by ADP were studied, in vivo T/C % of S-180 bearing ICR treated with ethyl ether(EE) layer of SMR, pulmonary colonization assay, changes of organ weight, WBC, number of platelet were evaluated experimentally and the results were obtained as follows: 1. The concentration inhibiting cell growth below 55% was 10~3g/ml of water layer and EE layer of SMR(ESR) against B16-Fo and 10-3g/ml of EE layer of SMR against A549. 2. Active compound isolated from Salviae miltiorrhizae Radix was identified as tanshion II A. 3. ED50 of tanshion II A was 0.8177 ㎍/㎖, 0.3431 ㎍/㎖, 1.3284 ㎍/㎖ and 0.8912 ㎍/㎖ against cancer cell lines as HCT15, XF498, SK-MEL-2, SK-OV-3, A549. 4. Tanshion II A induced DNA fragmentation of HL-60 from the concentration of 10 ㎍/㎖. 5. Solvent fractions of SMR showed the inhibitory effect on cell adhesion of A549 and B16-F0 most effectively specific to collagen Ⅳ. 6. Methanol and Ehtyl Ether extract of SMR inhibited platelet aggregation of ADP up to 35.6%, 46.1% at the concentration of 50 ㎍/㎖, 42.1%, 48.4% at the concentration of 100 ㎍/㎖ in the dose-dependent fashion. 7. T/c % ESR treated group was 143% based on the data that MST of ESR treated group was 22.6 days, while MST of control group was 15.7 days. 8. In pulmonary colonization assay ESR significantly inhibited pulmonary colonization of B16-Fo as compared with control group. 9. Gaining weight of lungs and spleen was significantly inhibited in ESR treated group, While the weight of kidney and liver was not signicantly changed as compared with control group. 10. ESR significantly decreased leukocytosis by B16-Fo to nomal range and significantly increased number of platelet as compared with control group. Above results indicate that Salviae miltiorrhizae Radix had antitumor effect and antitumor compound was indentified as tanshion ⅡA.
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