Anti-hepatoma activity and mechanism of ursolic acid and its derivatives isolated from Aralia decaisneana

瞄准：为了调查 ursolic (UA ) 和它的衍生物的反肿瘤活动，在肝细胞癌上从美┦木孤立 decaisneana 在试管内和在活体内。方法：在活体内细胞毒性被 3- 首先屏蔽[4,5-dimethylthiazol-2-yl ]-2, 5-diphenyltetrazolium 溴化物(MTT ) 试金。词法观察， DNA 梯子，流动血细胞计数分析，西方的污点和实时 PCR 被采用阐明 UA 的细胞毒素的机制。植入的老鼠肝细胞瘤 H22 被用来评估生长 UA 的禁止的效果在活体内。结果：UA 能显著地禁止 HepG2 和它的药抵抗的增长紧张， R-HepG2 房间，而是首先有教养的正常老鼠 hepatocytes 上的有的不禁止的效果而 UA 的所有六衍生物不能禁止所有的生长，测试房间排队。机制上的进一步的学习证明那 apoptosis 和 G0/G1 拘捕涉及多(自动数据处理核糖) 的细胞毒性和劈开聚合酶(PARP ) 。cyclooxygenase-2 (COX-2 ) 的 Downregulation 蛋白质并且在热吃惊蛋白质(HSP ) 的规定上面， 105 mRNA 相关到与 UA 对待的 HepG2 房间的 apoptosis。另外， UA 能也禁止 H22 肝细胞瘤在活体内的生长。结论：UA 是一个有希望的反肿瘤代理人，但是推进工作需要被做改进它的溶解度。

AIM： To investigate the anti-tumor activity of ursolic acid （UA） and its derivatives isolated from Aralia decaisneana on hepatocellular carcinoma both in vitro and in vivo. METHODS： In vivo cytotoxicity was first screened by 3-[4,5-dimethylthiazol-2-yl]-2, 5-diphenyltetrazolium bromide （MTT） assay. Morphological observation, DNA ladder, flow cytometry analysis, Western blot and real time PCR were employed to elucidate the cytotoxic mechanism of UA. Implanted mouse hepatoma H22 was used to evaluate the growth inhibitory effect of UA in vivo . RESULTS： UA could significantly inhibit the proliferation of HepG2 and its drug-resistance strain, R-HepG2 cells, but had no inhibitory effect on primarily cultured normal mouse hepatocytes whereas all the six derivatives of UA could not inhibit the growth of all tested cell lines. Further study on mechanism demonstrated that apoptosis and G0/G1 arrest were involved in the cytotoxicity and cleavage of poly-（ADP-ribose）- polymerase （PARP）. Downregulation of cyclooxygenase-2 （COX-2） protein and upregulation of heat shock protein （HSP） 105 mRNA correlated to the apoptosis of HepG2 cells treated with UA. In addition, UA also could inhibit the growth of H22 hepatoma in vivo. CONCLUSION： UA is a promising anti-tumor agent, but further work needs to be done to improve its solubility.