力达霉素抑制人纤维肉瘤肺转移的裸鼠活体成像观察

观察力达霉素 (LDM)、LDM与甲氨蝶呤 (MTX) 联合用药对人纤维肉瘤HT-1080^LUC实验性肺转移的抑制作用。构建稳定表达荧光素酶的HT-1080细胞株并扩增培养, 检测HT-1080^LUC细胞的荧光素酶的表达。建立裸鼠人纤维肉瘤HT-1080^LUC实验性肺转移模型, 并采用活体动物成像系统监测肿瘤的生长情况, 观察LDM和MTX的体内抗肺转移瘤活性。结果表明, HT-1080^LUC细胞荧光光子量与细胞数呈线性相关, 最小可检测的细胞数量为100个/孔。活体成像结果显示, 治疗组裸鼠的肺部荧光强度较对照组明显减弱。单独给予LDM 0.025 mg·kg^?1、LDM 0.05 mg·kg^?1或MTX 0.5 mg·kg^?1的肺转移抑制率分别为53.9%、75.9%和70.2%; LDM 0.025 mg·kg^?1与MTX 0.5 mg·kg^?1联合应用的肺转移抑制率为88.7%, 两药相互作用指数CDI = 0.82。研究表明, LDM对人纤维肉瘤肺转移有明显抑制作用, 与MTX联合用药对肺转移瘤的疗效明显优于单独给药。

Bioluminescence imaging evaluation of the inhibitory effect of lidamycin on lung metastasis of human fibrosarcoma in athymic mice

This study is to investigate the inhibitory effect of lidamycin (LDM) and its combination with methotrexate (MTX) on lung metastasis of fibrosarcoma by bioluminescence imaging in athymic mice.  A stable luciferase transfected HT-1080 cell line was constructed and the capability to establish experimental lung metastasis in athymic mice was confirmed.  The optical imaging system was applied to evaluate the formation of lung metastasis in vivo.  In addition, metastatic nodules were counted for the evaluation of inhibition rates.  As shown, the fluorescent intensity of luciferase-transfected HT-1080 cells was colinear with the cell population and the minimal detected cell population was 100 cells/well.  Optical imaging showed that the fluorescent intensity of treated group was apparently lower than that of the control.  The inhibition rates of lung metastasis by LDM alone at 0.025 mg·kg⁻¹ and 0.05 mg·kg⁻¹ were 53.9% and 75.9%, respectively, while that of MTX alone at 0.5 mg·kg⁻¹ was 70.2%.  The combination of LDM at 0.025 mg·kg⁻¹ and MTX at 0.5 mg·kg⁻¹ showed an inhibition rate of 88.7%.  The coefficient of drug interaction (CDI) was 0.82.  The results herein demonstrated that LDM alone had strong anti-metastasis effect on human fibrosarcoma HT-1080 and the inhibition efficacy is strengthened when combined with MTX.