Zhou Liang, Yang Yonghong, Luo Xiang, Gan Xinling, He Chengqi, Xia Yong, Zhu Siyi
Rehabilitation Medicine Center and Institute of Rehabilitation Medicine, West China Hospital, Sichuan University, 610041, Chengdu, China.
Key Laboratory of Rehabilitation Medicine in Sichuan Province, 610041, Chengdu, China.
J Cancer. 2025 Mar 31;16(7):2298-2311. doi: 10.7150/jca.105352. eCollection 2025.
: Chemotherapy is the mainstay treatment for metastatic triple negative breast cancer (TNBC). However, many patients still die of metastasis after chemotherapy, making it worthwhile to develop strategies to increase chemotherapy efficacy when treating metastatic TNBC. Previous studies have shown that exercise has the potential to inhibit breast cancer metastasis and enhance the effect of chemotherapy, and the level of exercise had a significant effect on tumor metastasis. However, the effect of different doses of exercise-referring to the combination of intensity and duration-on tumor metastasis during breast cancer chemotherapy remains unclear. : 4T1 TNBC subcutaneous tumors were treated with paclitaxel (PTX) and doxorubicin hydrochloride (DOX), as well as different intensities and duration of exercise. Tumor growth, survival, metastatic burden, and the frequencies of some important immune cells were measured to determine the effects, and underlying mechanism, of different exercise doses on the anti-cancer efficacy of PTX and DOX. : The combination of high-dose exercise with PTX and DOX promoted metastasis formation, shortened mouse survival, and up-regulated the neutrophil/T lymphocyte ratio in the lungs. In contrast, low-dose exercise synergized with PTX and DOX to suppress metastasis, prolonged the survival of mice, decreased the neutrophil/T lymphocyte ratio, and up-regulated the percentages of NK cells within the metastatic microenvironment. The combination of different exercise dose with PTX and DOX did not affect primary tumor growth. : The intensity and time of exercise might affect efficacy of PTX and DOX; however, TNBC patients should be careful concerning the intensity and time of exercises while undergoing chemotherapy. Breast cancer patients might be best served by participating in low levels of exercise, and avoiding excessive exercise, during PTX and DOX therapy.
化疗是转移性三阴性乳腺癌（TNBC）的主要治疗方法。然而，许多患者在化疗后仍死于转移，因此开发提高转移性TNBC化疗疗效的策略是值得的。先前的研究表明，运动有可能抑制乳腺癌转移并增强化疗效果，运动水平对肿瘤转移有显著影响。然而，不同剂量的运动（即强度和持续时间的组合）对乳腺癌化疗期间肿瘤转移的影响仍不清楚。用紫杉醇（PTX）、盐酸阿霉素（DOX）以及不同强度和持续时间的运动对4T1 TNBC皮下肿瘤进行治疗。测量肿瘤生长、生存期、转移负担以及一些重要免疫细胞的频率，以确定不同运动剂量对PTX和DOX抗癌疗效的影响及其潜在机制。高剂量运动与PTX和DOX联合促进转移形成，缩短小鼠生存期，并上调肺中的中性粒细胞/ T淋巴细胞比率。相反，低剂量运动与PTX和DOX协同抑制转移，延长小鼠生存期，降低中性粒细胞/ T淋巴细胞比率，并上调转移微环境中NK细胞的百分比。不同运动剂量与PTX和DOX联合不影响原发肿瘤生长。运动的强度和时间可能影响PTX和DOX的疗效；然而，TNBC患者在化疗期间应注意运动的强度和时间。在PTX和DOX治疗期间，乳腺癌患者最好进行低强度运动，避免过度运动。
