吐温80对温热抑瘤作用的增强效应——小鼠黑色素瘤实验研究

 目的: 研究吐温80合并41℃温热的抗肿瘤效应。方法: 接种B16黑色素瘤细胞至BALB/C小鼠不同部位建立荷瘤鼠模型, 观察荷瘤鼠死亡率、肿瘤生长曲线、血清肿瘤坏死因子和唾液酸的变化以及经血行转移的肺部瘤灶数的变化。结果: 吐温80合并41℃温热能明显地抑制小鼠黑色素瘤的生长, 延长荷瘤小鼠平均存活时间, 使肺部的转移瘤灶数大大降低；但吐温80和温热单独作用时均无此效果。荷瘤小鼠血清肿瘤坏死因子(sTNF)活性和唾液酸水平均明显高于正常BALB/C小鼠, 吐温80合并41℃、100分钟温热可显著降低sTFN活性, 并引起血清唾液酸水平的进一步升高。处理后第10周, 随着肿瘤的缩小, 唾液酸水平有明显的下降。结论: 吐温80能使温热在低于临界温度时即可发挥有效的抗肿瘤效应, 明显提高温热治疗的疗效和安全性, 是一较理想的温热合并药物。血清TNF和唾液酸的变化提示协同效应可能与肿瘤抗原的暴露和机体免疫抗肿瘤作用的活化亦有关。

The Synergic Effect Of Tween-80 on the Antitumor of Hyperthermia——Experimental Studeis of Mouse Melanoma

B16 Melanoma cells were inoculated into the BALB/C mice to establish melanoma-bearing models. The antitumor effect of Tween-80 in combination with hyperthermia 41°C was studied. We observed the changes of the mortality of tumor-bearing mice, the tumor growth curves, activities of serum tumor necrosis factor (sTNF) and the level of serum sialic acid (sSA) in tumor-bearing mice. The number of pulmonary metastatic tumor foci from blood flow was also detected. The results showed that combined with Tween-80, hyperthermia 41°C could dramatically suppress the growth of the melanoma in the feet of mice, survive the tumor-bearing mice and decrease the number of pulmonary metastatic tumor foci but no significant effects were observed by treatment with Tween-80 or hyperthermia at 41°C alone. The activities of sTNF and the level of sSA of the melanoma-bearing mice kept at higher levels than those of normal BALB/C mice. Tween-80 combined with heating 41°C significantly decreased the activities of sTNF and increased the level of sSA that decreased 10 weeks later with the tumor regression. These results demonstrate that Tween-80 may make hyperthermia exert effective antitumor effect below the critical temperature and increase the safety of hyperthermia in treatment. It is one of the most ideal synergist with hyperthermia. The changes of sTNF and sSA suggest that the synergetic effect could involve in facilitating the exposure of tumor antigen and activation of immune system.