Long term exposure to γ‑rays induces radioresistance and enhances the migration ability of bladder cancer cells.


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In Western countries, bladder cancer (BCa) is one of the most common types of malignancy, with highest incidence rate among urinary system malignancies. At present, as a strategy to preserve the quality and function of the bladder tissues, external-beam radiotherapy has been applied to an increasing number of patients with BCa, particularly the elderly and those in poor health. The onset of acquired radioresistance (ARR) during radiotherapy notably reduces the effectiveness of radiotherapy; however, the cause of ARR is unclear and remains untreatable. In order to investigate the mechanism of ARR, clinical fractionated irradiation was mimicked in vitro to obtain radioresistant BCa cells, 5637R, in the present study. Compared with the parental cell line, 5637R cells exhibited an increased distribution of S phase cells, enhanced migration ability and elevated levels of phosphorylated-STAT3, as determined using flow cytometry, cell migration analysis and western blotting, respectively. Furthermore, 5637R cells exhibited notable increases in extracellular signal-regulated kinase activation in response to ionizing radiation (IR) compared with 5637 cells. In addition, 5637R cells showed an early G(2)/M arrest within 8 h post-IR (18.23 +/- 3.85 vs. 6.42 +/- 3.82%, IR cells vs. control cells), whereas 5637 cells were arrested in G(2)/M phase 24 h post-IR (19.26 +/- 2.21 vs. 12.36 +/- 4.45%, IR cells vs. control cells). Overall, the present study suggested that phosphorylated STAT3 may be a potential biomarker to predict radioresistance and tumor recurrence in patients with BCa following conventional radiotherapeutic intervention. In addition, co-treatment with ERK inhibitor may be a viable approach to increase the anticancer efficacy of radiotherapy in patients with ARR; however, further investigation is required.
bladder cancer,migration,fractioned irradiation,radiosensitivity,mitogen-activated protein kinases
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