Modeling Principle

The Mouse DU145 Model is an internationally recognized gold-standard in vivo model for researching malignant proliferation, high invasion and metastasis, EMT progression, and chemoradiotherapy tolerance of human androgen-independent castration-resistant prostate cancer (CRPC). Derived from human prostate cancer brain metastatic lesions, DU145 cells are a classic advanced prostate cancer cell line with core phenotypes of androgen receptor negativity, hormone independence, high malignancy, strong invasion-metastasis ability and inherent chemoradiotherapy resistance, which faithfully recapitulate the pathological characteristics of clinically advanced, recurrent and metastatic castration-resistant prostate cancer with failed endocrine therapy. Compared with androgen-dependent cell lines such as LNCaP, DU145 cells are free from androgen regulation, presenting faster malignant progression, higher distant metastasis potential and more stable treatment-resistant phenotypes, serving as a benchmark cell line for advanced prostate cancer drug resistance, invasive metastasis, targeted pathway intervention and radiotherapy sensitization research. With stable adherent growth in vitro, negligible batch variation, high mycoplasma-negative rate and excellent in vivo tumorigenesis consistency, DU145 cells are widely utilized in prostate cancer malignant mechanism analysis, novel anti-tumor drug screening, chemoradiotherapy sensitization, invasion-metastasis blockade and drug resistance reversal research. Logarithmic-phase low-passage DU145 cells are subcutaneously inoculated into BALB/c-nu immunodeficient nude mice to establish standardized subcutaneous xenograft models with high tumorigenicity, stable tumor phenotypes, typical malignant characteristics and robust data reproducibility, fully meeting the standardized methodological writing requirements of NSFC projects, postgraduate proposals, dissertations and high-score SCI manuscripts.

Model Validation Criteria

Quantitative Criteria for Tumor Formation and Growth

1. Positive modeling criteria: Clear subcutaneous tumor nodules appear 4–6 days after DU145 cell inoculation. The tumor take rate is ≥95% within 10 days, and tumor volume ＞50 mm³ is defined as successful modeling. Tumors in the vehicle control group grow rapidly and continuously without spontaneous regression, which is completely consistent with the core characteristics of persistent proliferation and malignant progression of clinical advanced castration-resistant prostate cancer. 2. Reproducibility criteria: The intra‑group coefficient of variation (CV) of tumor volume in the vehicle group is ＜30%, indicating good modeling uniformity and low systematic error, which strictly meets SCI quality control requirements for data repeatability. 3. Pharmacodynamic response criteria: First-line prostate cancer positive drug intervention achieves TGI≥40% with significantly reduced tumor volume and weight compared with the control group (P＜0.05). The model presents stable and sensitive responses to chemotherapeutic drugs, targeted inhibitors and chemoradiotherapy sensitizers, enabling accurate evaluation of anti-proliferation, anti-invasion, drug resistance reversal and chemoradiotherapy sensitization effects on advanced prostate cancer.

Histopathological and Molecular Gold-Standard Indexes

1. HE gold standard: Tumor tissues consist of a large number of atypical prostate cancer cells with disordered cell size and morphology, large deeply stained nuclei, abundant mitotic figures, dense and disordered cell arrangement and significant atypia, which conform to the typical pathological morphological characteristics of human advanced prostate cancer. 2. Molecular phenotypic criteria: High Ki‑67 expression in tumor tissues indicates strong proliferative activity; high expression of Vimentin, N-cadherin, MMP2 and MMP9 combined with low E‑cadherin expression confirms significant EMT activation and high invasion-metastasis phenotype, while stably retaining core molecular characteristics of androgen independence and chemoradiotherapy tolerance, which highly recapitulate the pathological mechanism of malignant progression, invasion-metastasis and treatment resistance of clinical advanced CRPC. 3. Pharmacodynamic response criteria: Treatment groups show down-regulated Ki‑67 expression, up-regulated Cleaved‑Caspase‑3, recovered E‑cadherin and reduced expression of Vimentin/N-cadherin/MMP2/MMP9, confirming that drugs can effectively inhibit prostate cancer proliferation, promote apoptosis, reverse EMT, block invasion and metastasis, reverse chemoradiotherapy resistance and achieve chemoradiotherapy sensitization. 4. Evidence closed‑loop criteria: In vivo tissue detection results are highly consistent with in vitro DU145 cell mechanistic experiments, forming a complete and credible evidence chain of targeted intervention mechanisms.

Academic Evidence for Model Validity

The Mouse DU145 Model is an internationally recognized gold-standard in vivo model for research on advanced castration-resistant prostate cancer, androgen-independent malignant progression, high invasion-metastasis and chemoradiotherapy resistance mechanisms. Core validity evidence: ① Derived from clinical prostate cancer metastatic lesions, DU145 cells naturally lack androgen receptor signaling, perfectly simulating the CRPC pathological background of clinical endocrine therapy failure and disease progression; ② It presents rapid in vivo tumor formation, stable malignant phenotypes, constant EMT invasion and drug resistance phenotypes without batch drift, with excellent data reproducibility; ③ It has clear gradient pharmacodynamic responses to targeted pathway inhibitors, chemotherapy and radiotherapy sensitizers, serving as a core tool model for advanced prostate cancer translational medicine, drug resistance mechanism research and innovative drug development; ④ It exclusively covers the research dimensions of hormone-independent, metastatic and treatment-resistant prostate cancer, making up for the research shortcomings of early hormone-dependent prostate cancer models; ⑤ It has been widely accepted by top SCI journals in the field of urological oncology for decades. As a benchmark model for basic research, in-depth mechanism exploration and targeted translation of advanced prostate cancer, it is applicable for methodology construction of various projects, research proposals and high-score papers.

Model Advantages

The Mouse DU145 Model is an exclusive SCI gold-standard model for mechanism research and targeted drug development of advanced castration-resistant, metastatic and chemoradiotherapy-resistant prostate cancer. Core advantages: It accurately corresponds to clinically advanced CRPC prostate cancer with the worst prognosis and highest treatment difficulty, fully simulating the core pathological characteristics of clinical hormone therapy failure, malignant tumor proliferation, invasion-metastasis and chemoradiotherapy resistance. With extremely stable androgen-independent phenotype, high EMT activation degree and strong metastatic potential, it is the optimal model for simulating advanced refractory prostate cancer in vitro and in vivo. It features rapid and homogeneous in vivo tumorigenesis, minimal batch variation and high data signal-to-noise ratio, suitable for in-depth mechanism exploration of high-score SCI papers and innovative design of NSFC urological tumor projects. It can exclusively carry out characteristic research on hormone-independent progression, metastasis mechanism, chemoradiotherapy resistance reversal and targeted sensitization, filling the advanced tumor research gaps that cannot be covered by early prostate cancer models. With stable phenotypes and high academic recognition, it serves as the preferred benchmark system for mechanism research and drug screening in the field of urological tumors.

Research Applications

The Mouse DU145 Model is mainly applied to preclinical mechanism and translational research on hormone-independent progression, high EMT invasion and metastasis, chemoradiotherapy resistance, targeted sensitization and drug resistance reversal of advanced castration-resistant prostate cancer. Core application scenarios: molecular mechanism analysis of hormone-independent malignant proliferation in advanced CRPC prostate cancer; exploration of the mechanism by which core PI3K/AKT/STAT3 pathways drive tumor invasion, metastasis and treatment resistance; in-vivo efficacy evaluation of innovative targeted drugs, natural compounds and nano-formulations used alone or combined with chemoradiotherapy to achieve tumor suppression, anti-metastasis, sensitization and drug resistance reversal. It fills the research gap of standardized animal models for advanced refractory prostate cancer, fully supports innovative mechanism exploration for NSFC and provincial-level projects, postgraduate proposals, dissertations and high-score SCI papers in urological tumor research, serving as an indispensable core gold-standard in-vivo model for basic and targeted translational research of advanced metastatic and drug-resistant prostate cancer.

DU145 cell, human prostate cancer, castration-resistant prostate cancer, androgen-independent, high invasion and metastasis, radioresistance, EMT activation, nude mouse subcutaneous xenograft model, prostate cancer targeted therapy, chemoradiotherapy sensitization, preclinical efficacy evaluation