熱治療增強膀胱癌細胞對化療藥物cis-platinum的敏感度
陳宏恩1、張安辰2、陳栢均2、楊尚哲2、蔡德甫1、林宜佳1,4、仇光宇1、林致凡2、黃一勝1,2,3,4
1新光醫院 泌尿科、2新光醫院 中央研究室、3台北醫學大學 醫學院、4輔仁大學 醫學院
Hyperthermia enhances the sensitivity to cis-platinum in bladder cancer cells
Hung-En Chen 1, An-Chen Chang2, Po-Chun Chen2, Shan-Che Yang2, Te-Fu Tsai1, Yi-Chia Lin1, Kuang-Yu Chou1, Ji-Fan Lin2, and Thomas I-Sheng Hwang1,3,4,5
Department of Urology, Shin Kong Wu Ho-Su Memorial Hospital1, Central Laboratory, Shin Kong Wu Ho-Su Memorial Hospital2, Department of Urology, Taipei Medical University3, Division of Urology, School of Medicine, Fu-Jen Catholic University4, Taipei, Taiwan.
Background:
Bladder carcinoma (BC), the most common neoplasm of the urothelial tract, represents a high incidence and recurrence rates, as well as the limited advances in effective disease management. Cis-platinum has been used as standard first-line therapy in advanced or metastatic BC. However, high-dose cis-platinum associated complications are of great concern. Currently, hyperthermia is a widely discussed approach to cancer treatment, such as BC, cervical cancer and rectal cancer. In this study, we aim to analyze whether the combination of cis-platinum and hyperthermia treatment in BC has a greater anti-tumor effect than cis-platinum treatment alone. Therefore, the action of hyperthermia in affecting chemotherapy sensitivity was investigated.
Materials and Methods:
The bladder cancer cell lines T24 and 5637 or normal bladder epithelial cell line SV-HUC1 will be incubated with different doses of cis-platinum at 37℃ or 43℃ (hyperthermia) for 24 h. The in vitro cell viability and survival will be performed by AlamarBlue assay and clonogenic cell survival assay, respectively.
Results:
To examine the action of hyperthermia in affecting chemotherapy sensitivity, the AlamarBlue assay was performed to investigate the cell viability of BC cells. We found that the half-maximal inhibitory concentration (IC50) of cis-platinum is around 30 mM in both bladder cancer cell lines T24 and 5637. However, the combination of hyperthermia and cis-platinum treatment dramatically decreased IC50 (~15 mM). It indicates that hyperthermia enhances the sensitivity of cancer cells to cis-platinum. Moreover, results from the clonogenic cell survival assay confirmed that the synergistic action of the cis-platinum and hyperthermia was more cytotoxic to the cells than the single-agent chemotherapy. Most importantly, hyperthermia has no such effect in normal bladder epithelial cell line SV-HUC1. This demonstrates that hyperthermia is a potential adjuvant treatment, especially targeted to cancer cells.
Conclusion:
Taken together, hyperthermia enhances the sensitivity of BC cells to cis-platinum, which may reduce the commonly-used dosage of cis-platinum and thus decrease cis-platinum-associated complications in the human body. Furthermore, the combination of cis-platinum and hyperthermia treatment in BC has a greater anti-tumor effect than cis-platinum treatment alone.