Suppression of growth and hepatic metastasis of murine B16FO melanoma cells by a novel nutrient mixture
Suppression of growth and hepatic metastasis of murine B16FO melanoma cells by a novel nutrient mixture
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DOI：
10.3892/or_00000078
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发表时间：
2008-10-01
期刊：
影响因子：
4.2
通讯作者：
Niedzwiecki, Aleksandra
中科院分区：
文献类型：
--
作者：
Roomi, M. Waheed;Kalinovsky, Tatiana;Niedzwiecki, Aleksandra
高度转移性黑色素瘤对现有的治疗方法具有抵抗力。我们的主要目的是研究一种营养混合物(NM)对B16FO肿瘤生长和肝转移的影响。用5-6周龄裸鼠皮下接种10(6)B16FO黑色素瘤细胞，分别饲喂常规饲料和添加0.5%NM，观察裸鼠的肿瘤生长情况。四周后，处死小鼠，切除它们的肿瘤，称重，进行组织学处理。用10(6)B16FO黑色素瘤细胞经脾内注射，同时给予常规饲料或添加0.5%NM的饲料2周，对C57BL/6小鼠的转移进行了研究。对C57BL/6小鼠腹腔注射10(6)B16FO黑色素瘤细胞后的存活率进行了研究。然后在每周3次注射2 mg NM的基础上，常规、补充NNI或常规饮食。NM对B16FO黑色素瘤细胞生长的抑制作用为50%。两组的病变与恶性黑色素瘤一致。小鼠脾内注射B16FO细胞。那些喂食常规饮食的人出现了巨大的黑色脾和肝脏，表明脾内生长和肝脏转移。相比之下，补充NM的小鼠显示出较少的脾生长，但也减少了肝脏转移。NM和B16FO细胞腹腔注射对小鼠存活时间的影响。比喂食常规饮食的小鼠更大。为了证实NM对小鼠B16FO黑色素瘤细胞的作用，我们在体外观察了NM对小鼠B16FO黑色素瘤细胞的影响，包括用四甲基偶氮唑蓝比色法检测细胞增殖，苏木精伊红染色观察细胞形态，活绿caspase检测试剂盒检测细胞凋亡。在体外，100 mU g/ml的NM无毒性，500和1000 mU g/ml的NM毒性为对照组的44%，100 mU g/ml的H&E无明显变化，100 mU g/ml的NM诱导轻微的细胞凋亡，500 mU/ml的NM中度诱导细胞凋亡，1000 mU g/ml的NM引起广泛的细胞凋亡。
Highly metastatic melanoma is resistant to existing therapies. Our main objective was to investigate the effect of a nutrient mixture (NM) on B16FO tumor growth and hepatic metastasis. Tumor growth was studied in athymic nude male mice, 5-6 weeks old, inoculated with 10(6) B16FO melanoma cells subcutaneously and fed either a regular diet or one supplemented with 0.5% NM. Four weeks later, the mice were sacrificed and their tumors excised, weighed and processed for histology. Metastasis was studied in C57BL/6 mice, which received 10(6) B16FO melanoma cells by intrasplenic injection, as well as a regular or 0.5% NM-supplemented diet for 2 weeks. Survival was studied in C57BL/6 mice receiving 10(6) B16FO melanoma cells intraperitoneally (i.p.) followed by the regular, NNI-supplemented, or regular diet in addition to being administered with 2 mg NM injection 3 times per week. NM inhibited the growth of B16FO melanoma cells by 50%. Lesions in the two groups were consistent with malignant melanoma. Mice were injected with B16FO cells in the spleen. Those fed the regular diet developed large black spleens and livers indicating growth in the spleen and metastasis to the liver. In contrast, mice supplemented with NM showed less growth in spleen, but also reduced metastasis to the liver. The survival time of mice receiving NM supplementation and B16FO cells i.p. was greater than in mice which were fed the regular diet. To confirm effects in vivo, we investigated the effect of NM on murine B16FO melanoma cells in vitro, including cell proliferation by MTT assay, morphology by hematoxylin and eosin (H&E) staining and apoptosis using live green caspase detection kit. In vitro, NM was not toxic at 100 mu g/ml concentration, but exhibited 44% toxicity over the control at 500 and 1000,mu g/ml. H&E did not indicate any changes up to 100 mu g/ml. NM induced slight apoptosis at 100 mu g/ml, moderate at 500 and extensive at 1000 mu g/ml concentration.