Antitumor effect of polyphyllin D on liver metastases of neuroblastoma
Antitumor effect of polyphyllin D on liver metastases of neuroblastoma
复制标题
重植素D对神经母细胞瘤肝转移的抗肿瘤作用
DOI：
10.1007/s00383-022-05146-7
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发表时间：
2022
期刊：
影响因子：
--
通讯作者：
Suzuki T.
中科院分区：
文献类型：
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作者：
Kondo Y;Watanabe S;Naoe A;Takeuchi T;Niimi A;Suzuki M;Asai N;Okada S;Tsuchiya T;Murayama M;Yasui T;Inoue M;Suzuki T.
目的在体外实验中，我们报道了中药多叶黄的主要成分多叶黄素D对人神经母细胞瘤细胞具有抗癌作用。本研究的目的是研究聚叶根素D是否存在体内抗转移作用，建立神经母细胞瘤肝转移模型，并评价聚叶根素D的抗转移作用。方法采用人神经母细胞瘤细胞系IMR-32、LA-N-2和NB-69，分别在免疫缺陷BALB/c裸鼠和BALB/ rag -2/ jak3双缺陷（BRJ）小鼠身上建立皮下和腹腔肿瘤转移模型。为了评估多叶素D的活性，我们采用小鼠肝转移模型，通过尾静脉注射IMR-32细胞系。我们分析了磷酸缓冲液组和多叶绿素d组肝脏肿瘤的数量和面积。结果利用3种人神经母细胞瘤细胞系成功建立了免疫缺陷BRJ小鼠的银转移和腹腔内播散模型。在肝脏IMR-32细胞转移模型中，我们发现聚叶绿素D对转移灶数量和总面积均有抑制作用，且聚叶绿素D组的转移灶平均数量、平均病灶面积和裂解caspase-3阳性细胞数量均显著降低（p分别为0.016、0.020、0.043）。结论建立了神经母细胞瘤转移小鼠模型，首次证实了多叶绿素D对神经母细胞瘤肝转移具有抗肿瘤作用。
PurposeWe previously reported that polyphyllin D, a main component of the traditional Chinese medicinal herbParis polyphylla, exhibited anticancer effects in vitro against human neuroblastoma cells. The aims of this investigation was to examine the presence or absence of in vivo anti-metastasis effects of polyphyllin D were to establish a liver metastasis model of neuroblastoma and to evaluate the anti-metastasis effects of polyphyllin D.MethodsSubcutaneous and intraperitoneal tumors, and metastasis models were established in immune-deficient BALB/c nude and BALB/cRag-2/Jak3double-deficient (BRJ) mice using the human neuroblastoma cell lines IMR-32, LA–N-2, or NB-69. For evaluating polyphyllin D activity, we used a mouse model of liver metastasis with the IMR-32 cells line injected through the tail vein. We analyzed the livers number and area of liver tumors in of the phosphate buffer solution- and polyphyllin D-treated groups.ResultsLiver metastasis and intraperitoneal dissemination models were successfully established in immune-deficient BRJ mice using the three human neuroblastoma cell lines. In the liver metastasis, the model of IMR-32 cells, we found that polyphyllin D suppressed both the number and total area of metastatic foci the average number of metastatic foci, average focus areas, and number of cleaved caspase-3-positive cells were significantly lower in the polyphyllin D group (p= 0.016, 0.020, 0.043, respectively).ConclusionsWe developed a mouse models of neuroblastoma metastasis and demonstrated for the first time that polyphyllin D has an antitumor effect on neuroblastoma liver metastases.