PC Kz is the novel human prostate cancer model in vitro and in vivo

Abstract

BACKGROUND: The use of relevant in vitro and in vivo model systems is important in preclinical studies of anticancer agents. The process of creating tumor models is methodically complicated and has a number of disadvantages. Among tumor models of prostate cancer, the most accessible are 2D models (DU145, 22Rv1, PC3, LNCaP, VCaP cell lines), their xenograft models in immunodeficient mice and some patient-derived xenograft models. However, this panel of experimental models is not perfect and needs further expansion.

AIM: To create a new preclinical prostate cancer model, characterize it (morphology, tumorigenicity, tumor growth kinetics in vivo, verification of prostate-specific membrane antigen expression status, testosterone production, sensitivity to CYP17A1 inhibitors), and develop resistance to the steroid CYP17A1 inhibitor — abiraterone.

METHODS: CYP17A1 expression in PC Kz cell line was evaluated by reverse transcription polymerase chain reaction. Testosterone concentration was determined with an enzyme-linked immunosorbent assay. The sensitivity to antitumor agents was studied with the MTT test. Tumorigenicity was evaluated by transplantation of PC Kz cell line into Balb/c nude mice. The prostate-specific membrane antigen expression status was assessed using the indirect reaction of surface immunofluorescence.

RESULTS: The PC Kz cell line is characterized by a high level of CYP17A1 messenger RNA expression, comparable to that of the commercial 22Rv1 cell line. Immunophenotypic analysis demonstrated negative prostate-specific membrane antigen expression status of PC Kz cell line. A significant decrease (18%) in testosterone concentration in vitro was found, compared to the value in the control. This effect can be associated with the suppression of CYP17A1 gene expression.

The studied PC Kz cell line is tumorigenic in Balb/c nude mice (100% tumorigenicity was detected during the first passage at a transplantation dose of 107 cells/mouse). A pathomorphological study of the structures of the obtained subcutaneous PC Kz xenografts verified their identity to the histological image of human prostate cancer. Furthermore, PC Kz/AA cell line was obtained, resistant to abiraterone; the index of resistance was 3.4.

CONCLUSION: The derived PC Kz cell line was adapted for in vitro and in vivo growth, characterized by the main biological parameters, and can be recommended as an adequate test system to use in preclinical studies of new antitumor agents for the human prostate cancer treatment.

Keywords

prostate cancer / cell line / CYP17A1 inhibitor / resistance to anticancer agent

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Funding

Исследования по получению и изучению характеристик новой модели рака предстательной железы выполнены при финансовой поддержке гранта Министерства науки и высшего образования РФ от 28.09.2021г.Prostate cancer model characterization was supported by the Ministry of Science and Higher Education of the Russian Federation from 28.09.2021(075-15-2021-1060)

Исследования чувствительности полученной модели к химиотерапевтическим препаратам выполнены в рамках государственного задания Министерства науки и высшего образованияEvaluation of activity of anticancer agents has been supported by Ministry of Science and Higher Education, contract(075-01551-23-00 (FSSF-2023-0006).)

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