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Antitumor effect of polyphyllin D on liver metastases of neuroblastoma

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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.

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Funding

All authors have no funding of this study.

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Authors and Affiliations

  1. Department of Pediatric Surgery, Fujita Health University, 1-98 Dengakugakubo, Kutsukakecho, Toyoake, Aichi, 470-1192, Japan

    Yasuhiro Kondo, Shunsuke Watanabe, Atsuki Naoe, Tomonori Tsuchiya, Mika Murayama, Toshihiro Yasui, Mikihiro Inoue & Tatsuya Suzuki

  2. Department of Molecular Oncology, Fujita Health University, Toyoake, Japan

    Toshiyuki Takeuchi, Atsuko Niimi & Motoshi Suzuki

  3. Department of Pathology, Fujita Health University, Toyoake, Japan

    Naoya Asai

  4. Division of Hematopoiesis, Joint Research Center for Human Retrovirus Infection and Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan

    Seiji Okada

Authors
  1. Yasuhiro Kondo
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  2. Shunsuke Watanabe
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  3. Atsuki Naoe
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  4. Toshiyuki Takeuchi
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  5. Atsuko Niimi
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  6. Motoshi Suzuki
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  7. Naoya Asai
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  8. Seiji Okada
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  9. Tomonori Tsuchiya
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  10. Mika Murayama
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  11. Toshihiro Yasui
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  12. Mikihiro Inoue
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  13. Tatsuya Suzuki
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Contributions

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.

Corresponding author

Correspondence to Yasuhiro Kondo.

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Conflict of interest

All authors declare that they have no conflict of interest.

Ethical approval

This study was approved by our institutional review board (AP19142, DP19019).

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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

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