Radiosensitivity Enhancement by Arsenic Trioxide in Conjunction with Hyperthermia in the EC-1 Esophageal Carcinoma Cell Line

Abstract

Objective: To explore the effect on radiosensitivity of arsenic trioxide (As 2 0 3 ) in conjunction with hyperthermia on the esophageal carcinoma EC-1 cell line. Method: Inhibition of EC-1 cell proliferation at different concentrations of As 2 0 3 was assessed using the methyl thiazolyl blue colorimetric method (MTT method), with calculation of IC 50 value and choice of 20% of the IC 50 as the experimental drug concentration. Blank control, As 2 0 3 , hyperthermia, radiotherapy group, As 2 0 3 + hyperthermia, As 2 0 3 + radiotherapy, hyperthermia + radiotherapy and As 2 0 3 + hyperthermia + radiotherapy groups were established, and the cell survival fraction (SF) was calculated from flat panel colony forming analysis, and fitted by the 'multitarget click mathematical model'. Flow cytometry (FCM) was used to detect changes in cell apoptosis and the cell cycle. Results: As 2 0 3 exerted inhibitory effects on proliferation of esophageal carcinoma EC-1 cells, with an IC 50 of 18.7 μmol/L. After joint therapy of As 2 0 3 + hyperthermia + radiotherapy, the results of FCM showed that cells could be arrested in the G 2 /M phase, and as the ratio of cells in G 0 /G 1 and S phases decreased, cell death became more pronounced. Conclusion: As 2 0 3 and hyperthermia exert radiosensitivity effects on esophageal carcinoma EC-1 cells, with synergy in combination. Mechanistically, As 2 0 3 and hyperthermia mainly influence the cell cycle distribution of EC-1 esophageal carcinoma cells, decreasing the repair of sublethal damage and inducing apoptosis, thereby enhancing the killing effects of radioactive rays.

Fenofibrate Increases Radiosensitivity in Head and Neck Squamous Cell Carcinoma via Inducing G2/M Arrest and Apoptosis

“…Cells in the G2/M were most sensitive to irradiation and most resistant during the latter part of the S phase cell cycle (Cho et al, 2013) .Therefore, it is an effective strategy to increase the sensitivity of radiotherapy through inducing G2/M arrest (Hematulin et al, 2012;Cui et al, 2012). The cell cycle involves a series of events driven by cyclins and subsequent CDKs, which further activate transcription factor proteins for cell cycle progression from one phase to another.…”

“…The CDK1/cyclin B1 kinase complex plays a major role during G2/M transition. A reduction in CDK1/cyclin B1 kinase activity triggers G2/M cell cycle arrest (Cui et al, 2012;Khan et al, 2011). Accumulated evidence has suggested that a lot of radiosensitizing agents worked in different cancers such as taxol (Herscher et al, 1999), oxamate (Zhai et al, 2013) through inducing G2/M arrest via downregulation of cyclinB and CDK1.…”

“…It is widely known that cells are blocked in the G2/M phase during DNA damage, and cells are more susceptible to the cytotoxic effects of radiotherapy in the G2/M phase (Pawlik et al, 2004). Increasing irradiationinduced G2/M phase arrest allows cell death may be a strategy being employed in cancer therapeutics (Hematulin et al, 2012;Cui et al, 2012).…”

Effects of Thermotherapy on Th1/Th2 Cells in Esophageal Cancer Patients Treated with Radiotherapy

“…It is found that thermotherapy can enhance the efficacy of radiotherapy through its complementary effect on radiotherapy (Cui et al, 2012), direct effect on tumor cells (Wang et al, 2012;Zhou et al, 2012) and regulation of immune function. Thermotherapy targets cell membrane and cytoskeleton, while radiotherapy targets DNA, so the combined treatment can exert synergistic effect from different mechanisms (Saga et al, 2002;Bottaro and Liotta, 2003;Griffin et al, 2010;Dings et al, 2011).…”

Semi-Quantitative Exposure Assessment of Occupational Exposure to Wood Dust and Nasopharyngeal Cancer Risk

“…(Liorente et al, 2008). Other mechanisms also have been proposed such as repairing of sublethal damage and inducing apoptosis (Cui et al, 2012) or interleukin-18 promoter -607C>A polymorphism contributes to nasopharyngeal carcinoma risk: evidence from a meta-analysis including 1,886 subjects (Guo and Xia, 2013). The type of wood dust (soft wood or hard wood) was considered to be one of the factors related to wood dust carcinogenesis (IARC, 2012).…”