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不同热剂量局部热疗对小鼠黑色素瘤的疗效及其抗肿瘤免疫激发作用的比较研究
Therapeutic Effect of Hyperthermia at Different Thermal Doses on Melanoma in Mice and Its Stimulation on Anti-tumor Immunity
【摘要】 目的探讨既能有效杀伤肿瘤细胞又能最大限度激发抗肿瘤免疫的最适热剂量。方法体外实验采用MTT法检测不同热剂量(43℃30min和55℃10min)单次热疗及间隔24、48、72h的两次热疗对肿瘤细胞的杀伤作用。体内实验采用电热光聚焦加热灯对荷瘤小鼠移植瘤进行43℃及55℃局部热疗,观察不同热剂量对荷瘤小鼠的肿瘤生长、T细胞亚群及白细胞介素2(IL-2)的影响。结果体外实验显示热处理各组细胞存活率均明显降低,尤以55℃热疗最为显著。除了间隔72h的43℃两次热疗组外,重复热疗后细胞存活率均明显降低(P=0.000)。体内实验显示,肿瘤局部常规温度热疗(43℃30min)不能有效抑制荷瘤小鼠移植瘤生长,而高热热疗(55℃10min)在持续24天的观察中,与对照组和43℃热疗组相比肿瘤生长被明显抑制(P<0.05),且外周血CD4+T淋巴亚群比例和CD4+/CD8+比值以及IL-2水平均明显升高(P<0.05)。结论高温局部热疗较常规温度热疗更能有效地抑制肿瘤生长,并激发更强的抗肿瘤免疫。
【Abstract】 Objective To detect the therapeutic effect and the stimulation of the immunity reactions by heating primarily at different temperatures and find out the optimal thermal dose for local hyperthermia.Methods We heated the B16 cells in vitro by directly immersing 96-well plates into a temperature-controlled bath unit at 43 ℃ for 30 minutes or 55 ℃ for 10 minutes.The therapy was repeated in 24,48,or 72 hours.The proliferation of the cells was examined by MTT after heating.To detect the effect of hyperthermia on melanoma in vivo,36 melanoma-bearing mice were divided into control,43 ℃,and 55 ℃ groups randomly(12 in each).Half of the animals in each group were used to observe the growth of the tumor,and the rest of the mice were killed to detect the CD4+ and CD8+ T cells by Flow cytometry and serum IL-2 levels by ELISA.Results The in vitro experiments showed that the proliferation of the heated cells was significantly inhibited compared to the non-heated group.The 55 ℃ group achieved the lowest survival rate of the cells.The survival rate decreased significantly after a second heating therapy(P=0.000)in all the cells,except those that received the second treat after 72 hours at 43 ℃.The in vivo experiment revealed that the growth of the tumor was inhibited significantly in 55 ℃ group,comparing with the control and 43℃ groups(P<0.05).The ratio of CD4/CD8 and the serum IL-2 level increased after hyperthermia,especially in the 55 ℃ group(P<0.05).Conclusions Local hyperthermia can inhibit the growth of tumor and stimulate the anti-tumor immunity in mice.It is more effective than standard heating therapy.
【Key words】 Hyperthermia; Melanoma; Immunity reaction; T cell subset; IL-2;
- 【文献出处】 中国微创外科杂志 ,Chinese Journal of Minimally Invasive Surgery , 编辑部邮箱 ,2009年03期
- 【分类号】R739.5
- 【被引频次】15
- 【下载频次】223