西松烷型二萜对小鼠H22肝癌腹水瘤的抑制作用及其机制

INHIBITORY ACTION AND MECHANISM OF CEMBRANE-TYPE DITERPENES COLLECTED IN CERIOPS TAGAL ON MICE BEARING H22 ASCITIC TUMOR

目的研究西松烷型二萜对小鼠H22肝癌腹水瘤抑制作用,并初步探讨其作用机制。方法建立昆明小鼠H22肝癌腹水瘤模型,随机分为生理盐水组（Ⅰ组）、西松烷型二萜低剂量组（Ⅱ组）、中剂量组（Ⅲ组）、高剂量组（Ⅳ组）与环磷酰胺组（Ⅴ组）。建模后24 h开始给药,Ⅱ~Ⅳ组以不同剂量的西松烷型二萜连续灌胃给药7 d,对照组给予同体积生理盐水,Ⅴ组连续腹腔注射环磷酰胺7 d,末次给药24 h后处死半数动物。计算平均腹水量、腹水抑制率、腹水中瘤细胞数、瘤细胞存活率、细胞因子白细胞介素2（IL-2）、干扰素γ（IFN-γ）浓度。另一半小鼠继续观察生存状况,计算生存期及生存延长率。结果Ⅲ、Ⅳ组腹水量与Ⅰ组比较明显减少（F=28.37,q=2.91、4.76,P〈0.05）,腹水抑制率随药物剂量增加而升高。Ⅱ~Ⅳ组瘤细胞计数及瘤细胞存活率与Ⅰ组比较显著降低（F=7.21-19.13,q=2.92~4.76,P〈0.05）。Ⅱ~Ⅳ组小鼠平均生存期与Ⅰ组比较显著延长（F=35.77,q=2.91~4.75,P〈0.05）,延长率分别为20.21%、42.10%和51.02%。与Ⅴ组比较,Ⅱ、Ⅲ组小鼠在饮食、活动等方面状态较好。Ⅳ组用药期间食欲下降,活动少,停药后好转。Ⅱ~Ⅳ组IL-2和IFN-γ含量与Ⅰ组比较,差异均有显著性（F=21.17、35.47,q=2.93~4.77,P〈0.05）。结论西松烷型二萜对H22肝癌腹水瘤的生长具有明显的抑制作用,其机制可能与影响细胞免疫功能有关,其有可能开发成为一种新的海洋源性抗肿瘤药物。

Objective To study the inhibitory action and mechanism of cembrane-type diterpenes（CTD） collected in ceriops tagal on mice bearing H22 ascitic tumor. Methods A model of ascitic tumor in mice with hepatoma-22（H22） was created.All the models were randomized to five groups： group 1,normal saline group;group 2,low-dose CTD（5 mg/kg）;group 3,middle-dose CTD（10 mg/kg）;group 4,high-dose CTD（20 mg/kg）;group 5,cyclophosphamide（CTX 10 mg/kg）.Medication started at 24 hours after the models were created.Different doses of CTD were lavaged for mice in groups 2,3 and 4 for seven days,those in group 1 were given normal saline,and those in group 5,intraperitoneal CTX was administered for seven days.Half of the mice of each group were killed 24 hours after the last medication.The average volume of ascites,inhibition rate of ascites,tumor cell number and the cell survival rate,the levels of cytokine interleukin-2（IL-2） and interferon-γ（IFN-γ） in ascites were detected.The other half of the mice were continuely followed up for their living condition and life span. Results Compared with group 1,the volume of ascites in groups 3 and 4 reduced obviously（F=28.37;q=2.92,4.76;P0.05）,the inhibition rate of ascites increased with the increase of the dose of CTD.The number of tumor cells and survival rate in groups 2,3 and 4 were less than that in group 1（F=7.21-19.13;q=2.41-4.75;P0.05）.The mean survival duration of mice in groups 2,3 and 4 was longer than that in group 1,the extension rate was 20.21%,42.10% and 51.02%,respectively（F=35.77;q=2.91-4.76;P0.05）.In comparison with group 5,those in groups 2 and 4 were better in terms of the condition of eating,drinking,and activities.The appetide of mice in group 4 was poor and less activities during medication,but improved after drug withdrawal.The differences of levels of cytokine IL-2 and IFN-γ in ascites between groups 2,3,and 4 were significant（F=21.17,35.47;q=2.93-4.77;P0.05）. Conclusion The cembrane-type diterpenes has a significant inhibitory effect on mice brearing H22 ascitic tumor.Its mechanism may be associated with cellular immunity,which is likely to be a potential in the development of a novel marine anti-tumor drug.