力达霉素对小鼠结肠癌生长及其肝转移的抑制作用

Inhibitory Effect of Lidamycin on Growth of Colon Carcinoma 26 and Hepatic Metastasis in Mice

背景与目的:力达霉素(lidamycin,LDM,又称C鄄1027)是一种新型的具有烯二炔结构的抗肿瘤抗生素,在体内外对肿瘤具有显著抑制作用。本研究旨在观察力达霉素对小鼠结肠癌26皮下、盲肠、肝内、脾内移植瘤以及肝转移瘤的抑制作用。方法:小鼠结肠癌26移植于小鼠皮下、盲肠浆膜下(原位移植)、肝内等模型及脾内移植肝转移模型,力达霉素静脉给药一次,实验结束时计算力达霉素对移植瘤及肝转移瘤的抑制率,并应用图像分析系统分析肝转移病理切片。结果:0.025、0.05、0.1mg/kg力达霉素对皮下移植瘤的抑瘤率分别为64.8%、78.2%和94.2%,对盲肠移植瘤的抑瘤率分别为57.5%、71.5%和93.0%,对肝内移植瘤的抑瘤率分别为74.5%、82.3%和92.8%,对脾内移植瘤抑瘤率分别为9.2%、25.8%和70.2%;对肝转移灶的总抑制率分别为34.6%、50.7%和76.3%,对>2mm转移灶的抑制率分别为56.6%、56.7%和90.8%。用LEICAQWINV3图像分析系统分析肝转移病理切片,以肝脏病理切片中肿瘤转移面积占所检查肝脏病理切片总面积的比例作为评价指标,0.1mg/kg力达霉素对肝转移灶的抑制率为71.2%。结论:力达霉素明显抑制小鼠结肠癌26在皮下、盲肠、肝内和脾内移植瘤的生长,对肝转移灶也有显著抑制作用。

BACKGROUND & OBJECTIVE: Lidamycin (LDM, C-1027), an antitumor antibiotic containing a chromophore of enediyne structure, shows markedly cytotoxicities against cancer in vitro and in vivo. This study was to explore inhibitory effect of LDM on orthotopic transplanted tumors and hepatic metastasis of colon carcinoma 26 (C26) in mice. METHODS: A series of mice C26 models, including subcutaneous transplantation, orthotopic transplantation in cecum subserosa, intra-hepatic transplantation, and hepatic metastases after intra-splenic transplantation, were prepared and received intravenous injection of LDM 72 h after transplantation. Inhibitory rates of tumor growth and hepatic metastasis were calculated. LEICA QWINV3 image analysis system was used to determine the area of metastatic lesions in histopathologic sections. RESULTS: LDM at 0.025, 0.05, and 0.1 mg/kg inhibited the growth of subcutaneous tumors by 64.8%, 78.2%, and 94.2%, orthotopic tumors by 57.5%, 71.5%, and 93.0%, intra-hepatic tumors by 74.5%, 82.3%, and 92.8%, and intra-splenic tumors by 9.2%, 25.8%, and 70.2%, respectively. Determined by the numbers of metastatic nodules, LDM at 0.025, 0.05, and 0.1 mg/kg inhibited hepatic metastases from intra-splenic transplantation by 34.6%, 50.7%, and 76.3%, and larger metastatic lesions (> 2 mm) by 56.6%, 56.7%, and 90.8%, respectively. Evaluated by image analysis of metastatic lesions, LDM at 0.1 mg/kg inhibited hepatic metastases by 71.2%. CONCLUSION: LDM can inhibit growths of subcutaneous, orthotopic, and intra-hepatic transplanted tumors and hepatic metastases of murine colon carcinoma 26.