Abstract
Purpose
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.
Methods
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.
Results
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).
Conclusions
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.
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Availability of data and material
The data that support the findings of this study are available from the corresponding author, Yasuhiro Kondo, upon reasonable request.
References
Hishiki T, Matsumoto K, Ohira M et al (2018) Results of a phase II trial for high-risk neuroblastoma treatment protocol JN-H-07: a report from the Japan childhood cancer group neuroblastoma committee (JNEUROBLASTOMASG). Int J Clin Oncol 23:965–973. https://doi.org/10.1007/s10147-018-1281-8
Herve S, Ludovic D, Francois F et al (2012) Description of a new xenograft model of metastatic neuroblastoma using NOD/SCID/Il2rg Null (NSG) mice. In Vivo 26:19–30
Vassal G, Pondarre C, Cappeli C et al (1997) DNA-topoisomerase I, a new target for the treatment of neuroblastoma. Eur J Cancer 33(12):2011–2015. https://doi.org/10.1016/S0959-8049(97)00296-7
Vassal G, Terrier-Lacombe MJ, Bissery MC, Venaut AM et al (1996) Therapeutic activity of CPT-11, a DNA-topoisomerase I inhibitor, against peripheral primitive neuroectodermal tumour and neuroblastoma xenografts. Br J Cancer 74(4):537–545. https://doi.org/10.1038/bjc.1996.398
Dickson PV, Hanner B, Ng CYC et al (2007) In vivo bioluminescence imaging for early detection and monitoring of disease progression in a murine model of neuroblastoma. J Pediatr Surg 42(7):1172–1179. https://doi.org/10.1016/j.jpedsurg.2007.02.027
Sartelet H, Durrieu L, Fontaine F et al (2012) Description of a new xenofraft model of neuroblastoma using NOD/SCID/I12rg null (NSG) mice. In Vivo 26(1):19–29
Estelle D, Ludivine D, Valerie R et al (2014) Establishment and characterization of new orthotopic and metastatic neuroblastoma models. In Vivo 28(4):425–434
Estelle D, Ludvine D, Olivia B et al (2017) Dual inhibition using cabozantinib over comes HGF/MET signaling mediated resistance to pan-VEGFR inhibition in orthotopic and metastatic neuroblastoma tumors. Int J Oncol 50(1):203–211. https://doi.org/10.3892/ijo.2016.3792
Ono A, Hattori S, Kariya R et al (2011) Comparative study of human hematopoietic cell engraftment into BALB/c and C57BL/6 strain of rag-2/jak3 double-deficient mice. J Biomed Biotechnol. https://doi.org/10.1155/2011/539748
Lee MS, Yuet-Wa JC, Kong SK et al (2005) Effects of polyphyllin D, a steroidal saponin in Paris polyphylla, in growth inhibition of human breast cancer cells and in xenograft. Cancer Biol Ther 4:1248–1254. https://doi.org/10.4161/cbt.4.11.2136
Ong RC, Lei J, Lee RK et al (2008) Polyphyllin D induces mitochondrial fragmention and acts directly on the mitochondria to induce apoptosis in drug-resistant HepG2 cells. Cancer Lett 261:158–164. https://doi.org/10.1016/j.canlet.2007.11.005
Chen Y, Zhu J, Zhang W (2014) Antitumor effect of traditional Chinese herbal medicines against lung cancer. Anticancer Drugs 25:983–991. https://doi.org/10.1097/CAD.0000000000000127
Kong M, Fan J, Dong A, Cheng H, Xu R (2010) Effects of polyphyllin I on growth inhibition of human non-small lung cancer cells and in xenograft. Acta Biochim Biophys Sin 42:827–833
Watanabe S, Suzuki T, Hara F et al (2017) Polyphyllin D, a steroidal saponin in Paris polyphylla, induces apoptosis and necroptosis cell death of neuroblastoma cells. Pediatr Surg Int 33(6):713–719. https://doi.org/10.1007/s00383-017-4069-4
Li B, Yu B, Hui Y et al (2001) An improved synthesis of the saponin, polyphyllin D. Carbohydr Res 331:1–7. https://doi.org/10.1016/S0008-6215(01)00014-3
Rasband WS (1997–2012) ImageJ, U. S. National Institutes of Health, Bethesda, Maryland, USA. http://imagej.nih.gov/ij/
Schneider CA, Rasband WS, Eliceiri KW (2012) NIH image to imageJ: 25 years of image analysis. Nat Methods 9(7):671–675. https://doi.org/10.1038/nmeth.2089
Kanda Y (2013) Investigation of the freely available easy-to-use software ‘EZR’ for medical statics. Bone Marrow Transpl 48:452–458. https://doi.org/10.1038/bmt.2012.244
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All authors contributed to the study conception and design. Material preparation, data collection and analysis were performed by YK, SW, AN, TT, AN, MS, NA, SO, TT, MM, TY, MI, and TS. The first draft of the manuscript was written by YK and all authors commented on previous versions of the manuscript. All authors read and approved the final manuscript.
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Kondo, Y., Watanabe, S., Naoe, A. et al. Antitumor effect of polyphyllin D on liver metastases of neuroblastoma. Pediatr Surg Int 38, 1157–1163 (2022). https://doi.org/10.1007/s00383-022-05146-7
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DOI: https://doi.org/10.1007/s00383-022-05146-7