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Hyperthermia improves doxorubicin-based chemotherapy by activating mitochondrial apoptosis in bladder cancer
An-Chen Chang1, Po-Chun Chen2, Hung-En Chen3, Te-Fu Tsai4, Kuang-Yu Chou4, Chao-Yen Ho5, Thomas I-Sheng Hwang6
1 Translational Medicine Center, Shin Kong Wu Ho-Su Memorial Hospital, Taipei, Taiwan
2 Translational Medicine Center, Shin Kong Wu Ho-Su Memorial Hospital; Department of Life Science, National Taiwan Normal University, Taipei; Department of Medical Research, China Medical University Hospital, China Medical University, Taichung, Taiwan
3 Division of Urology, Department of Surgery, Shin Kong Wu Ho-Su Memorial Hospital, Taipei, Taiwan
4 Division of Urology, Department of Surgery, Shin Kong Wu Ho-Su Memorial Hospital, Taipei; Division of Urology, School of Medicine, Fu-Jen Catholic University, New Taipei City, Taiwan
5 Division of Urology, Department of Surgery, Shin Kong Wu Ho-Su Memorial Hospital; Institute of Traditional Medicine, School of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan
6 Division of Urology, Department of Surgery, Shin Kong Wu Ho-Su Memorial Hospital, Taipei; Division of Urology, School of Medicine, Fu-Jen Catholic University, New Taipei City; Department of Urology, Taipei Medical University, Taipei, Taiwan
Correspondence Address:
Thomas I-Sheng Hwang
Department of Surgery, Shin Kong Wu Ho-Su Memorial Hospital, Taipei, 11102
Taiwan
 Source of Support: None, Conflict of Interest: None
DOI: 10.4103/UROS.UROS_6_22
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Purpose: Although intravesical chemotherapy has several antitumoral benefits, it can also have severe side effects. The development of novel therapeutic approaches for bladder cancer (BC) is thus warranted. Hyperthermia (HT) is a widely applicable adjuvant therapy in various cancers. Therefore, this study investigated the effect of HT on improving the chemosensitivity of BC. Materials and Methods: The BC cell lines 5637 and T24 were cultured and treated with HT (43°C) for 24 h. Then, cell viability and survival were assessed using resazurin reagent and colony formation assay, respectively. Western blot assay was used to analyze the levels of Bax, Bcl-2, cleaved caspase-3, and cleaved poly (ADP-ribose) polymerase (PARP) protein expression. Mitochondria degradation was observed by MitoTracker Green staining. Results: In BC cells, HT co-administered with various concentrations of doxorubicin significantly inhibited cell viability and survival. Moreover, HT combined with doxorubicin promoted mitochondrial apoptosis, which caused Bax upregulation and Bcl-2 downregulation. Levels of cleaved caspase-3 and PARP protein expression were also elevated after co-treatment. Conclusion: Taken together, HT improved the chemosensitivity of BC cells to doxorubicin. HT combined with chemotherapy further activated mitochondrial apoptosis in BC cells. The findings suggested that HT may serve as a potential adjunctive treatment for BC that is ready to be applied clinically.
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