PC Kz is the novel human prostate cancer model in vitro and in vivo
- 作者: Sokolova D.1,2,3, Khan I.1,2, Zhdanov D.4,2, Demidova E.1, Krivchenko V.5, Aidossov C.2, Pokrovsky V.1,2,3
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隶属关系:
- N.N. Blokhin National Medical Research Center of Oncology
- Peoples’ Friendship University of Russia
- Sirius University of Science and Technology
- Institute of Biomedical Chemistry
- Moscow Institute of Physics and Technology
- 期: 卷 28, 编号 1 (2023)
- 页面: 37-52
- 栏目: Original Study Articles
- URL: https://journals.rcsi.science/1028-9984/article/view/217193
- DOI: https://doi.org/10.17816/onco562771
- ID: 217193
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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.
作者简介
Darina Sokolova
N.N. Blokhin National Medical Research Center of Oncology; Peoples’ Friendship University of Russia; Sirius University of Science and Technology
Email: v.pokrovsky@ronc.ru
ORCID iD: 0000-0003-3972-2425
SPIN 代码: 2960-4800
Cand. Sci. (Bio.)
俄罗斯联邦, 24 Kashirskoe shosse, Moscow 115478; Moscow; SochiIrina Khan
N.N. Blokhin National Medical Research Center of Oncology; Peoples’ Friendship University of Russia
Email: irinchek05@gmail.com
ORCID iD: 0000-0003-2948-0872
SPIN 代码: 6826-7694
Cand. Sci. (Bio.)
俄罗斯联邦, 24 Kashirskoe shosse, Moscow 115478;MoscowDmitry Zhdanov
Institute of Biomedical Chemistry; Peoples’ Friendship University of Russia
Email: zhdanovdd@mail.ru
ORCID iD: 0000-0003-4753-7588
SPIN 代码: 3845-2544
Dr. Sci. (Bio.)
俄罗斯联邦, Moscow; MoscowElena Demidova
N.N. Blokhin National Medical Research Center of Oncology
Email: badjito@mail.ru
ORCID iD: 0000-0002-6511-3423
俄罗斯联邦, 24 Kashirskoe shosse, Moscow 115478
Valery Krivchenko
Moscow Institute of Physics and Technology
Email: krivchenko.vo@phystech.edu
ORCID iD: 0009-0000-0807-1418
SPIN 代码: 6971-4087
俄罗斯联邦, Moscow
Chingis Aidossov
Peoples’ Friendship University of Russia
Email: aidossovchina@gmail.com
ORCID iD: 0009-0001-0034-8731
俄罗斯联邦, Moscow
Vadim Pokrovsky
N.N. Blokhin National Medical Research Center of Oncology; Peoples’ Friendship University of Russia; Sirius University of Science and Technology
编辑信件的主要联系方式.
Email: v.pokrovsky@ronc.ru
ORCID iD: 0000-0003-4006-9320
SPIN 代码: 4552-1226
MD, Dr. Sci. (Med.), Assistant Professor
俄罗斯联邦, 24 Kashirskoe shosse, Moscow 115478; Moscow; Sochi参考
- Yoshida GJ. Applications of patient-derived tumor xenograft models and tumor organoids. Journal of Hematology & Oncology. 2020;13(1). doi: 10.1186/s13045-019-0829-z
- Li Z, Bishop AC, Alyamani M, et al. Conversion of abiraterone to D4A drives anti-tumour activity in prostate cancer. Nature. 2015;523(7560):347–351. doi: 10.1038/nature14406
- Jorda R, Řezníčková E, Kiełczewska U, et al. Synthesis of novel galeterone derivatives and evaluation of their in vitro activity against prostate cancer cell lines. European Journal of Medicinal Chemistry. 2019;179:483–492. doi: 10.1016/j.ejmech.2019.06.040
- Norris JD, Ellison SJ, Baker JG, et al. Androgen receptor antagonism drives cytochrome P450 17A1 inhibitor efficacy in prostate cancer. The Journal of Clinical Investigation. 2017;127(6):2326–2338. doi: 10.1172/jci87328
- Oksala R, Moilanen A, Riikonen R, et al. Discovery and development of ODM-204: A Novel nonsteroidal compound for the treatment of castration-resistant prostate cancer by blocking the androgen receptor and inhibiting CYP17A1. The Journal of Steroid Biochemistry and Molecular Biology. 2019;192:105115. doi: 10.1016/j.jsbmb.2018.02.004
- Kwegyir-Afful AK, Ramalingam S, Ramamurthy VP, et al. Galeterone and The Next Generation Galeterone Analogs, VNPP414 and VNPP433-3β Exert Potent Therapeutic Effects in Castration-/Drug-Resistant Prostate Cancer Preclinical Models In Vitro and In Vivo. Cancers. 2019;11(11):1637. doi: 10.3390/cancers11111637
- Peehl DM, Badea CT, Chenevert TL, et al. Animal Models and Their Role in Imaging-Assisted Co-Clinical Trials. Tomography. 2023;9(2):657–680. doi: 10.3390/tomography9020053
- Chhikara BS, Parang K. Global cancer statistics 2022: the trends projection analysis. Chemical Biology Letters. 2023;10(1):451.
- Hirata E, Sahai E. Tumor Microenvironment and Differential Responses to Therapy. Cold Spring Harbor Perspectives in Medicine. 2017;7(7):a026781. doi: 10.1101/cshperspect.a026781
- Mezhevova IV, Sitkovskaya AO, Kit OI. Primary tumor cell cultures: сurrent methods of obtaining and subcultivation. South Russian Journal of Cancer. 2020;1(3):36–49. (In Russ). doi: 10.37748/2687-0533-2020-1-3-4
- Chen C, Lin W, Huang Y, et al. The Essential Factors of Establishing Patient-derived Tumor Model. Journal of Cancer. 2021;12(1):28–37. doi: 10.7150/jca.51749
- Jung J, Seol HS, Chang S. The Generation and Application of Patient-Derived Xenograft Model for Cancer Research. Cancer Research and Treatment. 2018;50(1):1–10. doi: 10.4143/crt.2017.307
- Caspar A, Mostertz J, Leymann M, et al. In Vitro Cultivation of Primary Prostate Cancer Cells Alters the Molecular Biomarker Pattern. In vivo. 2016;30(5):573–579.
- Freshney RI. Culture of Animal Cells: A Manual of Basic Technique and Specialized Applications. Moscow: BKL Publishers; 2018. (In Russ).
- Russell PJ, Kingsley EA. Human Prostate Cancer Cell Lines. In: Russel PJ, Jackson P, Kingsley EA, editors. Prostate Cancer. Methods and Protocols. Totowa, NJ: Springer; 2003. P:21–39. doi: 10.1385/1-59259-372-0:21
- Navone NM, Olive M, Troncoso P. Isolation and culture of prostate cancer cell lines. In: Langdon SP, editor. Cancer Cell Culture. Methods and Protocols. Totowa, NJ: Humana Press; 2004. P:121–132. doi: 10.1385/1592594069
- Peehl DM. Primary cell cultures as models of prostate cancer development. Endocrine-Related Cancer. 2005;12(1):19–47.
- Mosmann T. Rapid colorimetric assay for cellular growth and survival: application to proliferation and cytotoxicity assays. Journal of immunological methods. 1983;65(1-2):55–63. doi: 10.1016/0022-1759(83)90303-4
- Giatromanolaki A, Fasoulaki V, Kalamida D, et al. CYP17A1 and Androgen-Receptor Expression in Prostate Carcinoma Tissues and Cancer Cell Lines. Current Urology. 2019;13(3):157–165. doi: 10.1159/000499276
- Merhi Z, Buyuk E, Cipolla MJ. Advanced glycation end products alter steroidogenic gene expression by granulosa cells: an effect partially reversible by vitamin D. Molecular human reproduction. 2018;24(6):318–326. doi: 10.1093/molehr/gay014
- Sramkoski RM, Pretlow TG, Giaconia JM, et al. A new human prostate carcinoma cell line, 22Rv1. In Vitro Cellular & Developmental Biology – Animal. 1999;35(7):403–409. doi: 10.1007/s11626-999-0115-4
- Centenera MM, Vincent AD, Moldovan M, et al. Harvesting the heterogeneity of prostate cancer for target discovery using patient-derived explants. Cancers. 2022;14(7):1708. doi: 10.3390/cancers14071708
- Mezhevova IV, Shamova TV, Sitkovskaya AO, et al. Еxperience in сreating a primary culture of prostate cancer in vitro. Modern Problems of Science and Education. 2020;(5):26. (In Russ). doi: 10.17513/spno.30110
- Holmberg AR, Marques M, Lennartsson L, Meurling L, Nilsson S. Synthesis and binding of a novel PSMA-specific conjugate. Anticancer Research. 2018;38(3):1531–1537. doi: 10.21873/anticanres.12381
- Chen Z, Liu L, Xi X, et al. Aberrant H19 Expression Disrupts Ovarian Cyp17 and Testosterone Production and Is Associated with Polycystic Ovary Syndrome in Women. Reproductive Sciences. 2022;29(4):1357–1367. doi: 10.1007/s43032-021-00700-5
- Prilepskaya EA, Kovylina MV, Govorov AV. et al. Histological features of prostate cancer. Experimental & clinical urology. 2016;(4):56–58. (In Russ).