盐霉素聚合物颅内局部给药对大鼠胶质细胞瘤的治疗作用

A treatment study of 9L gliosarcoma in rats by the local delivery of salinomycinpolymer

目的探讨盐霉素对大鼠9L胶质肉瘤细胞系的体内、外生长和增殖的抑制作用。方法将盐霉素加入体外培养的大鼠9L胶质肉瘤细胞系中检测其对细胞生长、增殖活动的影响。对40只Fisher 344大鼠行颅内9L细胞注射,以制备载瘤大鼠模型。将盐霉素与可生物降解的药物基质聚酸酐类聚合物对羧基苯氧丙烷-癸二酸共聚物(p CPP∶SA)溶解并真空干燥后塑性,制成圆形药物聚合物颗粒。对载瘤大鼠行开颅手术,于瘤腔内植入聚合物颗粒,以观察盐霉素聚合物体内抗肿瘤效果,记录大鼠存活时间,进行进一步生存分析。结果盐霉素对9L细胞具有明显抑制作用,并表现出剂量依赖性特点。盐霉素聚合物颗粒具有良好生物相容性,能够短时间内稳定释放盐霉素进入局部组织。接受盐霉素聚合物治疗的大鼠,其中位生存期较对照组显著增加;采用30%盐霉素比例聚合物能够在延长大鼠生存时间的同时,降低盐霉素的使用剂量。结论盐霉素对9L胶质肉瘤细胞具有强大的抑制杀伤作用,采用盐霉素聚合物肿瘤局部给药的方式具有重大临床潜在研究和应用价值。

Objective To investigate the inhibition effect of salinomycin polymers on the growth and prolifer-ation of 9L gliosarcoma cells in vitro and in vivo.Methods Salinomycin was applied to the cultured 9L cell lines, and the growth and proliferation ability were tested 40 Fisher 344 rats were received intracranial injection of 9L cells. Polyanhydride polymers were composed with 1,3 -bis （p -carboxyphenoxy）propane （CPP）and sebacic acid （pCPP∶SA）,and contained salinomycin.The polymers were manufactured by mix -melt method and shaped into nbsp;round pills.The polymer complexes were implanted into the tumor cavitiesin vivo on the 5th day after tumor cell injec-tion.The rat survival time and histological characteristics were examined to compare the difference treatment condition of salinomycin polymers.Results Salinomycin could inhibit the growth and proliferation of 9L cells and showed a dose-dependent characteristic.The salinomycin polymers were biodegradable and could release salinomycin into the adja-cent tissue in a short time.Compared with the control group,the median survival time was increased significantly in sali-nomycin polymers group.The 30% salinomycin polymer could increased the median survival time of rats,as well as de-creased the dosage of salinomycin.Conclusion Salinomycin is an effective antitumor drug for the 9L gilosarcoma treatment.Local delivery of salinomycin polymer may be a promising method for the current clinical tumor treatment.