运动联合紫杉醇对小鼠乳腺癌移植模型荷瘤生长影响的研究

Effect of Exercise Conbined with Paclitaxel on Tumor Growth in 4T1Mouse Breast Cancer Model

目的：通过制备4T1小鼠乳腺癌移植模型,研究有氧运动、紫杉醇的单独及联合干预对小鼠4T1乳腺癌移植模型荷瘤生长的影响,并探讨其有关机制。方法：雌性6~8周龄BALB/c小鼠按体重随机分为正常对照组（N）和模型组。模型组小鼠接种4T1细胞。建模成功后,按体重、瘤大小分为生理盐水组（C）、紫杉醇组（P）、运动组（E）和联合组（EP）。P、EP组腹腔注射紫杉醇,剂量20mg/kg/w,其他组注射等体积生理盐水。运动强度采用17m/min,30min/次,5次/周,共5周。结果：1）EP组的瘤重、瘤体比、荷瘤体积均低于C组,差异显著（P〈0.05）。其他各组和C组相比,虽然瘤重低于C组,但均无显著性差异（P〉0.05）。2）P组、E组和EP组与C组相比,存活时间延长,有显著性差异（P〈0.05）。EP组与P组和E组相比,其延长生存时间的差异非常显著（P〈0.01）。3）与C组相比,EP组瘤细胞早、晚期凋亡比例增加,有显著性差异（P〈0.05）。4）与C组相比,EP组NF-κBp65的表达下降,差异非常显著（P〈0.01）,其他各组与C组相比无显著差异（P〉0.05）。各组IκBα的表达无显著差异（P〉0.05）。与C组和P组相比,E、EP组的Phospho-IκBα的表达下降,差异非常显著（P〈0.01）。结论：中强度运动联合紫杉醇能抑制小鼠乳腺癌移植模型荷瘤的生长,延长其生存时间。减少癌细胞IκBα的磷酸化,调节NF-κB的活性,促进瘤细胞的凋亡,可能是运动联合紫杉醇影响小鼠乳腺癌移植模型荷瘤生长的机制之一。

Objective：The aim of this research is to study the effect of exercise conbined with paclitaxel on tumor growth in 4T1 Mouse Breast Cancer Model and discuss the mechanism.Methods：Six-to eight-week-old female BALB/c mice were randomly assigned into two groups of normal control（N,8animals）and model.For the transplantable tumor model studies,0.8 ×105viable 4T1breast cancer cells were injected s.c.into the right axilla of BALB/c mice.5days after inoculation,the mice were randomized into four groups：（1）saline（C）,（2）paclitaxel-only（P）,（3）exercise-only in moderate-intensity（E）（4）exercise in moderate-intensity＋paclitaxel（EP）,16animals per group.The mice of P and EP group received i.p.injections of paclitaxel（20 mg/kg/w）during the whole experimental period.The mice of other groups received same volume of saline.Exercise groups performed progressive treadmill running up to 17m/min at 0% grade for 30minutes,5d/wk for 5weeks.Results：1）The weight of tumor,tumor volume and ratio of tumor weight and body weight of mice were significantly lower in EP group than C group（P0.05）.2）The survival time of mice was prolonged in the group of P,EP and E.The time was significantly longer in EP than other groups（P 0.01）.3）The rate of early and late apoptosis cells of mice were significantly higher in EP（P 0.05）.4）The expression of NF-κB p65was lower than C group（P0.01）,the expression of p-IκBαof mice was lower in EP（P0.01）than C and P group.Conclusion：Moderate intensity exercise combined with paclitaxel can effectively inhibit the growth of tumor,prolong the survival time with tumors in vivo for mice.One of mechanisms of exercise combined with paclitaxel may have a role in development of tumor is that induce apoptosis of tumor cells.