Establishment of a non-small-cell lung cancer-liver metastasis patient-derived tumor xenograft model for the evaluation of patient-tailored chemotherapy

Biosci Rep. 2019 Jul 5;39(7):BSR20182082. doi: 10.1042/BSR20182082. Print 2019 Jul 31.

Abstract

In order to optimize patient-tailored chemotherapy, a non-small-cell lung cancer (NSCLC)-liver metastasis patient-derived tumor xenograft (PDTX) model is developed. Computed tomography (CT)-guided NSCLC percutaneous biopsy was subcutaneously inoculated into the flank of non-obese diabetic/severe combined immunodeficiency (NOD/SCID) female mice (PDTX F1) and allowed to reach 500 mm3 volume. Then, the tumors were re-transplanted into Balb/c nude mice and liver metastasis was confirmed (PDTX F2), which were further assigned into doxorubicin (DOX), docetaxel (DTX), and non-treatment control group. H&E staining and Keratin 20 (CK20) staining were applied to determine the consistency of PDTX models and primary tumors. Tumor growth curve, body weight, and the expression of p65 nuclear factor (NF)-κB and the secretion of interferon (IFN)-γ were investigated. The successive transplant procedure can induce the NSCLC-liver metastasis PDTX model, and morphological and structural characteristics of PDTX models (F2) were in accordance with primary tumors. DOX and DTX could delay tumor growth, activate the NF-κB pathway, and promote IFN-γ secretion in the PDTX models. The NSCLC-liver metastasis PDTX model is established and provides a powerful mean to assess chemotherapeutic efficacy.

Keywords: DOX; DTX; Metastasis; NSCLC; PDTX.

MeSH terms

  • Animals
  • Carcinoma, Non-Small-Cell Lung / diagnostic imaging
  • Carcinoma, Non-Small-Cell Lung / pathology*
  • Cell Line, Tumor
  • Disease Models, Animal
  • Humans
  • Interferon-gamma / genetics
  • Liver Neoplasms / diagnostic imaging
  • Liver Neoplasms / pathology*
  • Liver Neoplasms / secondary
  • Lung Neoplasms / diagnostic imaging
  • Lung Neoplasms / pathology*
  • Mice
  • Mice, Nude
  • NF-kappa B / genetics
  • Neoplasm Metastasis
  • Tomography, X-Ray Computed
  • Xenograft Model Antitumor Assays

Substances

  • IFNG protein, human
  • NF-kappa B
  • Interferon-gamma