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Updated: May 16, 2026
Induction of Invasive Transitional Cell Bladder Carcinoma in Immune Intact Human MUC1 Transgenic Mice: A Model for Immunotherapy Development
Published on: October 30, 2013
Organoid transcriptomics identifies IFIT-associated immune modulation during cryptotanshinone treatment for cancer
Mengni Yang1, Shan Li2, Rui Li3
1School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, China; Sichuan Institute for Translational Chinese Medicine, Sichuan Academy of Chinese Medicine Sciences, Chengdu 610041, China.
Abstract:
Bladder cancer (BC), particularly muscle-invasive or metastatic disease, remains a major clinical challenge despite advances in immunotherapy. In this study, five candidate small molecules were screened, and cryptotanshinone (CTS) was identified as the most promising compound. Using BC cell lines and bladder tumor organoids, we evaluated the effects of CTS on proliferation, migration, apoptosis, and organoid growth. Transcriptomic sequencing of bladder tumor organoids, combined with protein-protein interaction analysis and public databases (TCGA-BLCA, TIMER, and TISIDB), was used to characterize CTS-associated molecular features. Integrative analyses identified IFIT1, IFIT2, and IFIT3 as representative interferon-stimulated candidate genes associated with BC progression, prognosis, immune infiltration, and PD-1/PD-L1 expression. These findings were supported by qRT-PCR and Western blot analyses showing reduced IFIT1/2/3 expression at both mRNA and protein levels following CTS treatment. Molecular docking suggested potential associations between CTS and interferon-related signaling proteins. Consistently, CTS reduced TBK1 and STAT1 phosphorylation, providing preliminary experimental support for its association with interferon-related signaling modulation. Collectively, CTS exerts growth-inhibitory effects and is associated with tumor cell-intrinsic interferon-related transcriptional and signaling changes in BC models, providing a basis for further investigation as a small-molecule candidate for BC.
Insights
Cryptotanshinone (CTS) shows promise in treating bladder cancer (BC) by inhibiting tumor growth and altering interferon-stimulated genes. This small molecule may offer a new therapeutic avenue for BC patients.
Area of Science:
- Oncology
- Molecular Biology
- Pharmacology
Background:
- Bladder cancer (BC), especially advanced stages, presents significant treatment challenges.
- Current immunotherapies have limitations for muscle-invasive or metastatic BC.
- Novel therapeutic strategies are urgently needed for bladder cancer.
Purpose of the Study:
- To identify and evaluate small molecules for bladder cancer treatment.
- To investigate the molecular mechanisms of cryptotanshinone (CTS) in BC models.
- To assess CTS's potential as a therapeutic agent for bladder cancer.
Main Methods:
- Screening of small molecules, identifying cryptotanshinone (CTS).
- In vitro and organoid studies assessing CTS effects on BC cell proliferation, migration, apoptosis, and growth.
- Transcriptomic sequencing, protein-protein interaction analysis, and public database integration (TCGA-BLCA, TIMER, TISIDB).
- Validation using qRT-PCR, Western blot, and molecular docking.
Main Results:
- CTS demonstrated significant anti-proliferative and anti-migratory effects on BC cells and organoids.
- Integrative analysis identified IFIT1, IFIT2, and IFIT3 as key interferon-stimulated genes linked to BC progression and immune infiltration.
- CTS treatment reduced IFIT1/2/3 expression and modulated interferon signaling pathways (TBK1, STAT1 phosphorylation).
Conclusions:
- Cryptotanshinone (CTS) exhibits growth-inhibitory effects in bladder cancer models.
- CTS influences tumor cell-intrinsic interferon-related gene expression and signaling.
- CTS represents a promising small-molecule candidate for further bladder cancer therapeutic development.