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. 2023 Feb;26(2):248-254.
doi: 10.22038/IJBMS.2022.67445.14780.

Preparation and application of patient-derived xenograft mice model of colorectal cancer

Yutao Zhang  1   2 , Yongming Yang  3   2 , Likun Zan  4 , Jing Wang  3 , Lei Yan  3 , Lili Zhao  3 , Lixia Chen  3 , Yanfeng Xi  4 , Wenqi Bai  1 , Xihua Yang  3
Affiliations

Preparation and application of patient-derived xenograft mice model of colorectal cancer

Yutao Zhang et al. Iran J Basic Med Sci. 2023 Feb.

Abstract

Objectives: Patient-derived xenograft (PDX) model becomes a more and more important tool for tumor research. This study aimed to establish a colorectal cancer PDX model and verify its applicability.

Materials and methods: Fresh human colorectal cancer tissue was surgically removed and subcutaneously inoculated into immunodeficient mice to establish the PDX model. Hematoxylin and eosin (HE) staining and immunohistochemical staining were used to evaluate the model. The successful PDX model was selected to study the efficacy of capecitabine in treating colorectal cancer.

Results: HE staining showed that the PDX mice model of colorectal cancer could preserve the histological characteristics of the primary tumor. Immunohistochemistry staining showed α-fetoprotein (AFP), carcinoembryonic antigen (CEA), and E-cadherin were strongly positively expressed in primary human and PDX tumor tissues, with a high degree of similarity. Capecitabine significantly inhibited PDX tumor growth and reduced the expression of AFP and CEA proteins in the tumor tissues (all P s<0.05).

Conclusion: We successfully established a colorectal cancer PDX model, and the PDX model could retain the histological and biological characteristics of the primary tumor. Using this PDX model, we revealed that capecitabine at a dose of 300-400 mg/kg can effectively treat colorectal cancer, and no significant difference in toxicity was found among different dose groups. The current work provides a feasible framework for establishing and validating the PDX tumor model to better facilitate the evaluation of drug efficacy and safety.

Keywords: Alpha-fetoproteins; Cadherins; Capecitabine; Carcinoembryonic antigen; Colorectal neoplasms; Heterografts.

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Conflict of interest statement

The authors have declared that no competing interests exist.

Figures

Figure 1
Figure 1
HE staining and immunohistochemical staining of AFP, CEA, and E-cadherin in primary tumor tissue (P0) and P2 generation PDX tumor tissue
Figure 2.
Figure 2.
Capecitabine suppressed tumor growth in mice inoculated with P2 generation PDX tumor
Figure 3
Figure 3
Capecitabine altered the pathological structure and expressions of Ki67 and E-cadherin in tumor tissues of the PDX mice
Figure 4
Figure 4
Capecitabine down-regulated AFP and CEA protein expression levels in tumor tissues of the colorectal cancer PDX model
See this image and copyright information in PMC

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