| PurposeThe aim of this research is to study the effect of aerobic exercise of different intensity, paclitaxel and the combination of them in the treatment period of breast cancer, to explore its possible mechanism by establishing4T1mouse breast cancer model, in order to provide experimental basis for enriching the treatment means of breast cancer and expanding the application range of exercise in the prevention and treatment of breast cnncer.MethodsSix to eight-week-old female BALB/c mice were randomly assigned into two groups of normal control (N,8animals) and model (96animals).For the transplantable tumor model studies, viable4T1breast cancer cells were injected s. c. into the right axilla of BALB/c mice.5days after inoculation, the mice were randomized into six groups:①saline-only (C),②paclitaxel-only(P),③exercise-only in low-intensity (E1),④exercise-only in moderate-intensity(E2),⑤exercise in low-intensity and paclitaxel (EP1),⑥exercise in moderate-intensity and paclitaxel (EP2), with16animals per group. The mice of P, EP1and EP2group received i.p. injections of paclitaxel (20mg/kg/w) during the whole experimental period. The mice of other groups received same volume of saline. Exercise groups performed progressive treadmill running up to12m/min or17m/min at0%grade for30minutes,5d/wk for5weeks.Results1. viable4T1breast cancer cells were injected s. c. into the right axilla of BALB/c mice.5days after inoculation, all mice bore tumor. Model was successfully established. The pathological examination revealed that there was invasive breast cancer. All receptors of estrogen, progestoner, human epidermal growth factor receptor--2are negative.2. After inoculation, the weight of mice loss. The weight of mice in each group of model were significantly lower than weight of mice in N group. There were no significant difference in weight between model mice.3. The survival time of mice was prolonged in the group of P,EP1, EP and E2, The time was significantly longer in EP2than other groups.4. The weight of tumor^tumor volume and ratio of tumor weight and weight of mice were significantly lower in EP2group than C group. There were no significantly difference between other groups and C group.5. The percentage of regulatory T cell in lymphnode of mice was significantly higher in model groups than N group. The percentage of regulatory T cell in tumor and lymphnode of mice were significantly lower in EP2group than C and P group.6. The expression of transforming growth factor-β1and interleukin10of mice were significantly lower in EP2.7. The percentages of S phase was significantly lower and rate of early and late apoptosis cells of mice were significantly higher in EP2.8. The expression of nuclear factor-kappaB p65. phospho-inhibitory subunit of κB-α of mice were lower in EP2. The expression of p-IκBα of mice was also lower in EP1and E2group, and the effect on p-IκB was better in EP1and EP2than P group, moreover, the effect on p-IκB was better in E2than E1group.Conclusion1. The survival time of mice was longer in E2,17m/min moderate intensity exercise can prolong the survival time with tumors in vivo for mice. 2.17m/min moderate intensity exercise combined with paclitaxel can effectively inhibit the growth of tumor, the intervention effect of exercise,paclitaxel alone is ineffective.17m/min moderate intensity Exercise may enhance the anti-cancer effect of paclitaxel.3. One of mechanisms of exercise combined with paclitaxel may have a role in tumor growth is that exercise may down-regulated the expression of NF-κ Bp65and P-IκBα, reduce proliferation of tumor cells, reduce the percentage of regulatory T cell in tumor and lymphnode of mice, weaken the immune escape of tumor cells, induce apoptosis of tumor cells.
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