Tween-80在体内、外对温热抗肿瘤作用的影响

The antitumor effects of Tween-80 combined with hyperthermia in vivo and in vitro

目的 研究Tween 80在体内外与 41℃温热协同对B16黑色素瘤细胞的抗肿瘤作用及机理 ;方法 将B16黑色素瘤细胞接种至BALB/C小鼠 ,建立荷瘤鼠模型 ,观察Tween 80与 41℃温热作用后荷瘤鼠死亡率、存活时间、肿瘤生长曲线以及经血行转移的肺部瘤灶数的变化 ;用免疫组织化学方法 ,观察B16细胞在Tween 80与 41℃温热作用后即时、4小时和 72小时 ,c fos、Ubiquitin(Ub)表达的改变 ,进行定量分析 ;结果 Tween 80合并 41℃温热能明显地抑制荷瘤小鼠黑色素瘤的生长 ,延长荷瘤小鼠平均存活时间 ,使荷瘤小鼠死亡率显著下降 ;小鼠肺部转移瘤灶数降低有极显著意义 ;但Tween 80和温热单独作用时均无此效果。免疫组织化学染色显示Tween 80与 41℃温热合并作用后 4小时 ,c fos、Ub表达明显增加 ,并持续至 72小时 ,其它各组经测定均无显著变化。结论 Tween 80能使温热在低于临界温度时即发挥有效的抗肿瘤效应 ,明显提高温热的抗肿瘤效应 ,可成为一种较理想的温热抗肿瘤协同药物。其协同机制可能与诱导肿瘤细胞凋亡有一定关联。

Objective To investigate the antitumor effect and synergic mechanism of Tween-80 in combination with hyperthermia 41℃?Methods B16 melanoma cells were inoculated into the BALB/C mice to establish melanoma-bearing models.The changes of the mortality and survival of tumor-bearing mice as well as the tumor growth curves were observed.The number of pulmonary metastatic tumor foci from blood flow was also measured.The expression of c-fos and Ubiquitin oncoproteins in B16 cells was studied by immunocytochemistry at 0 hour,4-hour and 72-hour after treatment respectively.Results Hyperthermia 41℃ combined with Tween-80 could dramatically suppress the growth of the melanoma in the feet of mice,survive the tumor-bearing mice and decrease the metastatic tumor foci in the lungs of tumor-bearing mice.The expressions of c-fos and Ubiquitin were obviously increased by combined treatment (P<0.05,P<0.01).But no significant effects were observed by treatment with Tween-80 or hyperthermia at 41℃ alone.Conclusion These results demonstrate that Tween-80 may make hyperthermia exert effective anti-tumor effect below the critical temperature and increase the safety of hyperthermia in treatment.It is one of ideal synergist with hyperthermia.It is suggested that synergetic antitumor effect of Tween-80 with heating could be involved in apoptosis of B16 melanoma cells.