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

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

  • Int J Hyperthermia. 2024;41(1):2316085. doi: 10.1080/02656736.2024.2316085.
Ying Xu 1,  Guoliang Sun 2,  Tiantian Yang 3,  Huaibiao Li 1,  Poyi Hu 4,  Wanru Luo 3,  Tingke Zhang 5,  Haoran Liu 6,  Guoyi Chen 7,  Zhangqun Ye 8,  Yuqing Wu 9,  Jie Yu 10,  Wanyi Chen 1,  Kai Zhao 1,  Chunyan Liu 1,  Huiping Zhang 1
Affiliations

Affiliations

  • 1 Institute of Reproductive Health, Tongji Medical College, Huazhong University of Science and Technology, Hubei, China.
  • 2 Department of Urology, the First Affiliated Hospital, School of Medicine, Zhejiang University, Zhejiang, China.
  • 3 College of Pharmacy, Hubei University of Science and Technology, Hubei, China.
  • 4 Department of Cardiovascular Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Hubei, China.
  • 5 Wuhan Britain-China School, Hubei, China.
  • 6 Bio-X, Stanford University School of Medicine, Stanford, CA, USA.
  • 7 Department of Urology, Jianyang First Hospital, Fujian, China.
  • 8 Department of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Hubei, China.
  • 9 Suzhou OptoMedic Technologies Inc, Jiangsu, China.
  • 10 School of Life Science and Technology, Wuhan Polytechnic University, Hubei, China.
PMID: 38346911 DOI: 10.1080/02656736.2024.2316085
Abstract

Objective: 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.

Keywords

Hyperthermia chemotherapy; NMIBC; RT4; bladder cancer; organoids.

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