Albaconol的抗肿瘤活性及对DNA拓扑异构酶Ⅱ的影响

目的　研究地花菌提取物Albaconol的体内外抗肿瘤活性及对DNA拓扑异构酶Ⅱ (TOPOⅡ )活性的影响。方法　以人白血病细胞株K5 6 2、人乳腺癌细胞株Bcap 37、人胃腺癌细胞株BGC 82 3和人非小细胞肺癌细胞株A5 4 9为模型 ,采用MTT法测试Albaconol对肿瘤细胞增殖的影响 ;以小鼠移植性肉瘤S180 和小鼠移植性肝癌H2 2 为模型 ,检测Al baconol静脉给药对肿瘤生长的影响 ;以 pBR32 2DNA为底物 ,采用琼脂糖凝胶电泳法测定Albaconol对肿瘤细胞DNATOPOⅡ活性的影响。结果　Albaconol对K5 6 2、Bcap 37、BGC 82 3、A5 4 9的半数抑制浓度 (IC50 )分别为 (2 4 2±1 77)、(1 88± 1 4 1)、(1 0 4± 0 6 4 )、(1 18± 1 10 )mg·L-1;Albaconol0 87、1 73、3 4 6mg·kg-1剂量组对S180 生长的抑制百分率 (抑瘤率 )分别为 2 8 2 %、4 3 2 %、4 7 4 % ;对H2 2 的抑瘤率分别为 15 6 %、2 2 4 %、37 8% ;Albaconol能明显影响DNATOPOⅡ的活性 ,表现为促进其介导的DNA解旋或断裂 ,并抑制其介导的DNA再连接反应。结论　Alba conol具有较强的体内、外抗肿瘤活性 ,DNATOPOⅡ是其抗肿瘤作用的细胞内靶点之一。

Study on the antitumor activity of Albaconol and its effect on DNA topoisomerase Ⅱ

Aim To study the antitumor activity of Albaconol fro mAlbatrellus confluensand its effect on DNA topoisomerase Ⅱ (TOPO Ⅱ) activity. Methods The cytotoxicity of Albaconol on human leukemia K-562 , breast carcinoma Bcap-37, gastric adenocarcinoma BGC-823 and lung adenocarcinoma A549 cell lines were determined by MTT assay and the results were expressed as IC 50 values. The inhibitory effect of Albaconol on tumor growth was observed by the models of implanted sarcoma 180 (S 180) and hepatoma 22 (H 22) in mice and the results were expressed as inhibitory rate of tumor growth. The effect of Albaconol on TOPO Ⅱ activity was measured by agarose gel electrophoresis using Plasmid pBR322 DNA as the substrate. Results The results showed that the IC 50 values of Albaconol on K562, Bcap-37, BGC-823 and A549 cell lines were (2.42±1.77),(1.88±1.41),(1.04±0.64) and (1.18±1.10) mg·L -1, respectively. The inhibitory rates of tumor growth at doses of 0.87,1.73,3.46 mg·kg -1 of Albaconol on S 180 and H 22 were 28.2%,43.2%,47.4% and 15.6%,22.4%,37.8%,respectively. Albaconol influenced obviously DNA TOPO Ⅱ activity , stimulated DNA cleavage and inhibited DNA reunion mediated by TOPO Ⅱ. Conclusion Albaconol exhibited significant antitumor activity in vitroand in vivo,and DNA TOPO Ⅱ is one of the targets oriented by Albaconol.