Validation of hyperthermia as an enhancer of chemotherapeutic efficacy: insights from a bladder cancer organoid model

Autor: Ying Xu, Guoliang Sun, Tiantian Yang, Huaibiao Li, Poyi Hu, Wanru Luo, Tingke Zhang, Haoran Liu, Guoyi Chen, Zhangqun Ye, Yuqing Wu, Jie Yu, Wanyi Chen, Kai Zhao, Chunyan Liu, Huiping Zhang
Jazyk: angličtina
Rok vydání: 2024
Předmět:
Zdroj: International Journal of Hyperthermia, Vol 41, Iss 1 (2024)
Druh dokumentu: article
ISSN: 02656736
1464-5157
0265-6736
DOI: 10.1080/02656736.2024.2316085
Popis: AbstractObjective This study aimed to evaluate the combined efficacy of hyperthermia and chemotherapy using a bladder cancer organoid model and to explore hyperthermia-related molecular pathways.Method Tumor organoids were generated by embedding RT4 bladder cancer cells into Matrigel. The resulting organoids were treated with pirarubicin or gemcitabine at 37 °C or 42 °C. Proliferation was determined by Ki67 immunofluorescence staining, and apoptosis was assessed using a TdT-mediated dUTP nick end labeling (TUNEL) assay. RNA sequencing was used to identify the differentially expressed genes.Results Bladder cancer organoids were successfully established and exhibited robust proliferative abilities. Treatment with gemcitabine or pirarubicin under hyperthermic conditions caused pronounced structural damage to the organoids and increased cell death compared to that in the normothermically treated group. Furthermore, Ki67 labeling and TUNEL assays showed that the hyperthermia chemotherapy group showed a significantly reduced proliferation rate and high level of apoptosis. Finally, RNA sequencing revealed the IFN-γ signaling pathway to be associated with hyperthermia.Conclusion Overall, hyperthermia combined with chemotherapy exerted better therapeutic effects than those of normothermic chemotherapy in grade 1-2 non-muscle-invasive bladder cancer, potentially through activation of the IFN-γ-JAK-STAT pathway.
Databáze: Directory of Open Access Journals
Externí odkaz: