Establishment of childhood hepatoblastoma xenografts and evaluation of the anti-tumour effects of anlotinib, oxaliplatin and sorafenib

Pediatr Surg Int. 2022 Mar;38(3):465-472. doi: 10.1007/s00383-021-05043-5. Epub 2022 Jan 15.

Abstract

Background: Hepatoblastoma (HB) is a common primary malignant liver tumour in children, mainly treated by means of traditional chemotherapy using platinum and doxorubicin (ADM). There has been limited progress in the research and development of new drugs for treating HB.

Methods: A tumour biopsy from a child with HB was implanted into immunodeficient mice. The primary tumour and patient-derived xenograft (PDX) tumour were extensively characterised by histology, immunohistochemistry (IHC), and humanisation identification. We used the PDX model to evaluate the anti-tumour effects of anlotinib oxaliplatin (L-OHP) and sorafenib on childhood HB.

Results: The established PDX model maintained the histological characteristics of the primary tumour. Anlotinib, L-OHP, and sorafenib can significantly inhibit the tumour growth in the PDX model. There was no obvious damage of the drugs to the heart, liver and kidney of the mice, and the side effects observed were light.

Conclusion: We have successfully established a PDX model of childhood HB. The model retains important molecular characteristics of human primary tumours. Using the model, it was found that anlotinib, L-OHP, and sorafenib have a good inhibitory effect on the growth of childhood HB. This provides a preliminary research basis for the clinical application of the drugs.

Keywords: Anlotinib; Childhood hepatoblastoma (HB); Oxaliplatin; Patient-derived xenograft (PDX); Sorafenib.

MeSH terms

  • Animals
  • Hepatoblastoma* / drug therapy
  • Heterografts
  • Humans
  • Indoles
  • Liver Neoplasms* / drug therapy
  • Mice
  • Oxaliplatin
  • Quinolines
  • Sorafenib

Substances

  • Indoles
  • Quinolines
  • anlotinib
  • Oxaliplatin
  • Sorafenib