Department of Pediatric Surgery, Fujita Health University, 1-98 Dengakugakubo, Kutsukakecho, Toyoake, Aichi, 470-1192, Japan.
Department of Molecular Oncology, Fujita Health University, Toyoake, Japan.
Pediatr Surg Int. 2022 Aug;38(8):1157-1163. doi: 10.1007/s00383-022-05146-7. Epub 2022 Jun 14.
We previously reported that polyphyllin D, a main component of the traditional Chinese medicinal herb Paris 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.
Subcutaneous and intraperitoneal tumors, and metastasis models were established in immune-deficient BALB/c nude and BALB/c Rag-2/Jak3 double-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.
Liver 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).
We developed a mouse models of neuroblastoma metastasis and demonstrated for the first time that polyphyllin D has an antitumor effect on neuroblastoma liver metastases.
我们之前报道过，重楼属植物中的主要成分重楼苷 D 对体外培养的人神经母细胞瘤细胞具有抗癌作用。本研究旨在观察重楼苷 D 是否具有体内抗转移作用，建立神经母细胞瘤肝转移模型，并评价重楼苷 D 的抗转移作用。
采用免疫缺陷 BALB/c 裸鼠和 BALB/c Rag-2/Jak3 双缺陷（BRJ）小鼠皮下和腹腔肿瘤及转移模型，用人神经母细胞瘤细胞系 IMR-32、LA-N-2 或 NB-69 建立。为了评价重楼苷 D 的活性，我们使用 IMR-32 细胞系经尾静脉注射的小鼠肝转移模型。我们分析了磷酸盐缓冲液和重楼苷 D 处理组的肝脏肿瘤数量和面积。
我们成功地在免疫缺陷 BRJ 小鼠中使用三种人神经母细胞瘤细胞系建立了肝转移和腹腔播散模型。在 IMR-32 细胞的肝转移模型中，我们发现重楼苷 D 抑制了转移灶的数量和总面积，平均转移灶数量、平均灶面积和 cleaved caspase-3 阳性细胞数量均显著低于重楼苷 D 组（p=0.016、0.020、0.043）。
我们建立了神经母细胞瘤转移的小鼠模型，首次证明重楼苷 D 对神经母细胞瘤肝转移具有抗肿瘤作用。
