運動預適應不影響阿黴素抗癌功效並減緩其所引起心毒素之研究

Exercise Preconditioning Does Not Affect Antitumor Activities of Doxorubicin and Mitigate Doxorubicin-Induced Cardiotoxicity

陳美莉(Mei-Li Chen) ； 連家瑩(Chia-Ying Lien)

《臺大體育學報》 33輯 (2017/09) Pp. 19-31

https://doi.org/10.6569/NTUJPE.2017.33.03

摘要

因為抗癌藥物阿黴素的心毒性非常強烈，因此醫生在臨床上使用阿黴素治療癌症都必須審慎處理。先前的研究顯示運動預適應能減緩阿黴素的心毒性，但是這些研究大都是使用非荷瘤動物，因此運動預適應有可能會降低阿黴素的抗癌功效。本研究旨在探討1.運動預適應是否會干擾阿黴素抗癌功效。2.運動預適應是否能減緩阿黴素所引起的心毒性。研究方法如下：8 週大的C57BL / 6 公小鼠隨機分配到不運動組或運動組。兩週的運動訓練後，在皮下組織注射5×105 的黑色素腫瘤細胞或相同容量的生理食鹽水。三週後，在小鼠的腹腔注射12毫克/公斤的阿黴素或注射相同容量的生理食鹽水。在注射阿黴素10 天後，用心臟超音波檢查小鼠的心臟功能。研究結果發現，1.阿黴素可以有效的抑制癌細胞成長。2.運動訓練無法提升或影響阿黴素抗癌的功效。3.阿黴素會造成心壁變薄，注射阿黴素對非荷瘤動物心臟的傷害反而還比荷瘤動物來得大。4.阿黴素會造成心臟功能減退，運動可以減緩阿黴素所造成的心毒素傷害。

關鍵字

阿黴素 ； 心毒性 ； 運動預適應

並列摘要

Cardiotoxicity of doxorubicin (DOX) is the major concern in clinical used. Previous studies have showed that exercise preconditioning attenuates DOX-induced cardiac dysfunction in murine. However, those studies were using non-tumor bearing animals. Therefore, exercise preconditioning might also reduce its anticancer activities. PURPOSE: To investigate that whether exercise preconditioning will disturb DOX antitumor activities. If antitumor activities of DOX did not be impeded, would exercise preconditioning also has cardioprotection to against DOX. METHODS: Eight week old C57BL/6 male mice were randomly assigned to sedentary (SED, n=35) or treadmill exercise (TM, n=9) groups. After two weeks of exercise training (5ds/wks, 1 hrs/day), animals were a subcutaneous Injection of either 5x10^5 cells of B16F10 (SED+Tumor, n=19 or TM+Tumor, n=9) or an equivalent volume of saline (SED+Nontumor, n=16). Three weeks after the tumor injection, animal were received either 12 mg/kg of DOX (S+NT+D, n=8; S+T+D, n=10; T+T+D, n=9) or an equivalent volume of saline (CON, n=8; S+T+S, n=9). Ten days after completing DOX treatment cardiac function was assessed by echocardiography. RESULTS: DOX treatment resulted in a significant reduction in tumor growth (S+T+D, 3.9±1.3g; S+T+S, 10.7±2.5g; p＜.05). Treadmill running does not affect DOX antitumor activities (T+T+D, 2.7±2.0g; P＞.05). DOX treatment for tumor group significant declined in mitral flow velocity MV (544±36 cm/s) and aortic velocity AV (395±25 cm/s) values and a significant increase in isovolumic relaxation time IVRT (28.1±1.5ms) values, when compare with control group. Although, MV (572±52 cm/s) and IVRT (25.9+1.0 ms) of T+T+D group were also significant different from CON group. However, AV (474±21mm/s) of T+T+D group is not significant different with CON group (P＞.05). CONCLUSIONS: DOX does reduce tumor growth. And treadmill running does not affect DOX antitumor activities. In fact, the treadmill running not only suppresses DOX antitumor activities but also attenuate DOX-induced cardiac dysfunction.

並列關鍵字

doxorubicin ； cardiotoxicity ； exercise preconditioning

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