化學熱療對於膀胱癌之治療益處: 提升泛艾黴素吸收並調節腫瘤微環境

徐志豪^1#、游家豪^1#、溫玉清^1,2、林雍偉^1,2

1.臺北市立萬芳醫院-委託臺北醫學大學辦理, 泌尿科

2.臺北醫學大學醫學院泌尿學科

Therapeutic Benefits of Chemohyperthermia: Boosting Epirubicin Uptake and Modulating the Tumor Microenvironment in Bladder Cancer

Chih-Hao Hsu^1#, Chia-Hao You^1#, Yu-Ching Wen^1,2, Yung-Wei Lin^1,2

1 Department of Urology, Wan Fang Hospital, Taipei Medical University, Taipei, Taiwan.

2 Department of Urology, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan

Purpose:

Chemohyperthermia gained attention as an alternative to the standard treatment with BCG instillation for bladder carcinoma in situ (CIS). This study aims to evaluate the effectiveness of chemohyperthermia by enhancing the uptake of Epirubicin and regulating anti-tumor immune responses in patients with bladder cancer.

Materials and Methods:

In vitro analyses were conducted using human bladder cancer cell lines (BFTC-905 and T24) obtained from the American Type Culture Collection. Epirubicin-treated cells were incubated at 37°C and 42°C, and various assays were employed to assess cell cycle protein expressions, growth rates, and cytokine activity. Fluorescence microscopy and flow cytometry evaluated intracellular drug uptake, while western blot and ELISA assessed protein and cytokine levels associated with immune modulation. Animal models analyses focused on changes in the tumor immune microenvironment and immune cell activation status.

Results:

Fluorescence imaging revealed chemohyperthermia a substantial increasing in Epirubicin uptake in cells exposed to 42°C environment with significant inhibition of cancer cell colony formation. The western blot analysis indicated elevated cleaved-PARP levels. Hyperthermia also boosted c-Jun phosphorylation. Additionally, chemohyperthermia promoted the expression of HSP70 and elevated levels of IL-6 and TNF-α, which were positively correlated with infiltration of anti-tumor immune cells (CD8+ cytotoxic T cells, M1 macrophages, and NK cells) while suppressing regulatory T cells and immunosuppressive M2 macrophage.

Conclusion:

The findings demonstrate that chemohyperthermia significantly enhances the sensitivity of bladder cancer cells to Epirubicin by increasing intracellular drug uptake and activating anti-tumor immune responses, providing a promising treatment strategy for bladder CIS.