羟基喜树碱联合低分子肝素钠对肿瘤生长转移抑制的研究

 目的　研究羟基喜树碱（HCPT）联合低分子肝素钠对裸小鼠肝细胞癌生长转移的抑制作用。方法 建立人肝癌裸鼠转移模型。将造模成功的40只模型鼠随机分成4组，即对照组、HCPT组、低分子肝素钠组、联合组（HCPT、低分子肝素钠）。分别观察肿瘤大小、抑瘤率，测血清甲胎蛋白（AFP）、肿瘤微血管密度（MVD）、血小板内皮细胞黏附分子-1（CD31）。结果　对照组、HCPT组、低分子肝素钠组、联合组的肿瘤体积分别为（25 260±12 976）mm3、（5773±2498）mm3、（5911±3093）mm3和（1596±1207）mm3；抑瘤率分别为0、76.6 %、79.8 %和94.1 %；MVD分别为21.1±6.5、17.2±3.1、7.1±2.3和4.8±1.8；CD31分别为31.7±6.1、26.2±5.2、20.9±4.7和19.5±2.4；AFP分别为（121.9±31.4）ng／ml、（56.2±37.9）ng／ml、（75.6±28.7）ng／ml和（20.7±12.9）ng／ml；肝癌转移率分别为80 %、70 %、20 %和10 %；肺转移率分别为70 %、60 %、20 %和10 %；腹壁转移率分别为90 %、60 %、30 %和30 %；腹腔积液形成率分别为20 %、10 %、0和0。HCPT组、低分子肝素钠组、联合组分别与对照组比，对肝癌生长的抑制作用差异有统计学意义（F＝9.074，P＜0.01）。HCPT联合低分子肝素钠对肝癌的生长和转移有良好的抑制作用，与对照组及HCPT组比较差异有统计学意义（F＝24.837，P＜0.01）。结论　HCPT联合低分子肝素钠对肿瘤的生长与转移有良好的抑制作用。

Anti-tumor effects of 10-hydroxycamptothecinc combined with low molecular weight heparins

Objective To study the inhibition effects of 10- hydroxycamptothecinc and low molecular weight heparins on human hepatocellular carcinoma(HCC) in nude mice. Methods Metastatic model of HCC was established in nude mice. The model mice were randomly divided into 4 groups: the control group, 10-hydroxycamptothecinc group, low molecular weight heparins group, and combined treatment group (10- hy－droxycamptothecinc and low molecular weight heparins). Tumor sizes, tumor inhibition rates, tumor metas－tases, intratumoral microvessel density (MVD), CD31 and AFP were evaluated. Results In comparison with the control group and the 10-hydroxycamptothecinc group, the tumor sizes of the low molecular weight heparins and the combined treatment group were significantly smaller; the tumor inhibitor rates were 0 versus 76.6 %, 79.8 %, 94.1 %; MVD were 21.1±6.5 versus 17.2±3.1, 7.1±2.3 and 4.8±1.8; CD31 were 31.7±6.1 versus 26.2±5.2, 20.9±4.7 and 19.5±2.4; the incidence of liver metastasis was 80 % versus 70 %, 20 % and 10 %; lung metastasis was 70 % versus 60 %, 20% and 10 %; the peritoneal metastasis was 90 % versus 60 %, 30 % and 30 %. AFP were （121.9±31.4）ng/ml versus（56.2±37.9）ng/ml,（75.6±28.7）ng/ml and （20.7±12.9）ng/ml.Inhibiting effects of growth and metastasis of HCC in 10- hydroxycamptothecinc group, low molecular weight heparins group and combined treatment group were significantly different from those of the control group (F =9.074, P ＜0.01), combined treatment inhibited the angiogenesis in the tumors more effectively than that in control and other groups(F ＝24.837，P ＜0.01). Conclusion 10-hydroxycamptothecinc combined low molec－ular weight heparins can inhibit tumor growth and metastasis by inhibiting tumor angiogenesis in nude mice HCC model.