药物干预小鼠凝血功能对肿瘤形成的影响

Effects of anticoagulation drug on the development of tumor in mice

目的:以药物干预接种肿瘤小鼠凝血功能,研究早期肿瘤形成与凝血系统功能的关系。方法:成年健康KM小鼠皮下接种S180肿瘤细胞,分正常组、肿瘤对照组、肝素组、抗癌药组、溶剂组。接种瘤细胞后第5天开始药物干预,分别为:不处理、皮下注射生理盐水(2 d 1次)、皮下注射低分子量肝素(2 d 1次)、抗癌药灌胃(每d 1次)、溶剂灌胃(每d 1次)。在接种后第3周末测量肿瘤大小、凝血酶原时间、血浆抗凝血酶Ⅲ和血清TNF-α水平,再处死小鼠,剥离实体肿瘤。统计学分析肿瘤大小与各检测参数之间的相关性。结果:肿瘤对照组和溶剂组分别在接种瘤细胞后第6和第10天有1小鼠死亡,肿瘤大小测量结果显示,对照组和溶剂组的瘤体显著较大,平均为(5.0±2.5)cm^2,肝素组的外观比前两者略小,平均为(3.2±1.8)cm^2,但与前两者无统计学上差异。抗癌药组瘤体显著较小,平均(1.8±0.82)cm^2,与对照组有显著差异(P<0.01)。统计学分析结果显示,肿瘤大小与凝血酶原时间和抗凝血酶Ⅲ水平成负相关(P<0.05),但与血清TNF-α的水平成正相关(P<0.05)。结论:单纯肝素干预治疗肿瘤小鼠无显著减小肿瘤大小作用,但与对照组相比瘤体有缩小的趋向,抗凝药物治疗可能对肿瘤的发生和发展具有抑制作用。

Aim：To investigate the relationship between the early carcinogenesis and the function of coagulation system by using anticoagulation and anticancer drugs. Methods： KM mice were or were not inoculated with cancer cells S180 and then divided into 5 groups, normal （without cancer）, control, heparin, DL507 （anticancer drug combination） and solvent （solvent for the anticancer drug）. After 5 days of cancer cell inoculation, the mice were treated as ： no drug for normal group, peritoneal saline for control, peritoneal low molecular weight heparin for heparin group, oral DI507 for the anticancer drug group and oral solvent for solvent group. At the end of the third week after cancer cell inoculation, the size of tumor, the thrombinogen time （TI＇）, plasma antithrombin III （ATIII） and serum TNF-α were determined, and then the mice were sacrificed and the tumors were isolated from the mouse bodies. Correlations of the tumor size with the determination parameters were analyzed by Peason test. Results： One mouse died in each of the control and solvent group at day 6 and day 10 after inoculation, respectively. The average size of tumor was found to be （5.0 ± 2. 5 ） cm^2 for the control, （3.2±1.8 ） cm2 for the hep-arin group, and （ 1.8 ± 0. 82） cm2 for the DI507 group. Statistic analysis showed that the tumor size was negatively correlated with TT and ATIII （ P 〈 0. 05 ）, but positively with serum TNF-α level （ P 〈 0. 05 ）. Conclusion：There was no significant difference in tumor size between the control and the heparin group, but the latter showed a trend for inhibition of tumor development, and thus antielotting therapy might play an inhibitory role in the development of cancers.