中国红树科植物角果木中Dolabrane型二萜的抗肿瘤作用

ANTI-TUMOR EFFECT OF Dolabrane DITERPENES IN THE MANGROVE PLANT CERIOPS TAGAL

目的探讨中国红树植物角果木中Dolabrane型二萜Tagalsins A的抗肿瘤作用及其初步作用机制。方法建立小鼠H22肝癌实体瘤及H22肝癌腹水瘤模型,随机分为Tagalsins A高、中、低剂量组（20、10、5 mg.kg-1）、生理盐水组（空白对照）、环磷酰胺组（CTX 10 mg.kg-1）,每组小鼠各10只。建模24 h后开始给药,Tagalsins A各剂量组给予Tagalsins A连续灌胃7 d,对照组灌胃给予同体积生理盐水,CTX组连续腹腔给予CTX7 d。末次给药24 h后处死动物,计算抑瘤率、生命延长率、脏器指数;流式细胞术测细胞凋亡率。结果 TagalsinsA各剂量组小鼠H22实体瘤生长较空白对照组明显减慢（F=8.90,q=3.31~6.52,P〈0.01）。Tagalsins A低、中、高剂量组的抑瘤率分别为24.49%、35.37%、48.30%,其中Tagalsins A中、高剂量组抑瘤作用与CTX组比较差异无显著性（q=2.85、1.01,P〉0.05）。Tagalsins A明显延长H22腹水瘤小鼠生存时间（F=17.06,q=5.45~11.26,P〈0.01）;降低小鼠的胸腺指数（F=21.82,P〈0.01）,而升高肝脏指数（F=121.84,P〈0.01）。Tagalsins A各组肿瘤细胞的凋亡率较空白对照组明显升高（F=127 7.68,q=51.11~82.02,P〈0.01）。结论 Dolabrane型二萜Tagalsins A对小鼠H22移植瘤的生长具有明显的抑制作用,其机制可能与诱导细胞凋亡有关。

Objective To study the anti-tumor effect of Dolabrane diterpenes（Tagalsins A） of the mangrove plant ceriops tagal and its mechanism. Methods Models of solid tumor of hepatoma-22（H-22） and ascitic tumor of H-22 were created.All the models were randomized to five groups： high-dose,medium-dose,and low-dose Tagalsins A groups（5,10 and 20 mg·kg-1,respectively）,saline group and CTX group（10 mg·kg-1）,with 10 mice in each group.The Tagalsins A was given through intragastric administration,the CTX through intraperitoneal injection for 7 days,the same volume of saline was given to the control group.The mice were killed 24 hours after the last medication,the tumor inhibition rate（TIR）,life-prolong rate,organ index,and apoptosis rate were calculated. Results Compared with NS group,the growth of H-22 solid tumors in the mice of different-dose tagalsins A groups was significantly inhibited（F=8.90;q=3.31-6.52;P0.01）.The TIR in low-,medium-,and low-dose groups were 24.49%,35.37%,and 48.30%,respectively,in which,the differences of TIR among medium-,high-dose,and CTX group were not significant（q=2.85,1.01;P0.05）.Tagalsins A significantly prolonged the survival of H-22 ascites tumor-bearing mice（F=17.06;q=5.45-11.26;P0.01）,reduced the thymus index（F=21.82,P0.01）,while elevated liver index（F=121.84,P0.01）.The rates of apoptosis of tumor cells in Tagalsins A groups were higher than that in the NS group（F=127 7.68,q=51.11-82.02,P0.01）. Conclusion Tagalsins A manifests an important effect on inhibition of the growth of transplanted H-22 in mice,the mechanism might be related to apoptosis of inducer cells.