Development and characterization of an isogenic cell line with a radioresistant phenotype

Abstract

In this model, the emergence of radiation resistance was associated with the acquisition of biological traits that support more aggressive behaviour of cancer cells. We have generated a model that will be useful for mechanistic studies and development of rational treatments against radiation resistance in cancer.

Gli-1/PI3K/AKT/NF-kB pathway mediates resistance to radiation and is a target for reversion of responses in refractory acute myeloid leukemia cells

“…The DNA damage response pathway triggers gene transcription to repair the damage, and unrepaired DNA damage leads to apoptosis. Many previous reports have demonstrated an increase in the capacity to repair DSBs, the main type of DNA damage induced by ionizing radiation [29, 30], as well as reduced apoptosis in radiation-resistant sublines compared with the radiosensitive parent line [31, 32]. Because Hh signaling regulates many genes involved in DNA repair processes, targeting Hh signaling has the potential to increase sensitivity to radiotherapy.…”

X-Ray Induced Mutation Frequency at the <i>Hypoxanthine Phosphoribosyltransferase</i> Locus in Clinically Relevant Radioresistant Cells

“…Several reports suggest that radioresistance is associated with the enhanced repair of radiation-induced DNA damage [1] [7] [18] [19]. Our previous study also showed that X-ray-induced phosphorylated histone H2AX (γH2AX) foci disappear more rapidly in HepG2-8960-R than in parental HepG2 [1].…”

“…The molecular basis of radioresistance remains to be elucidated. The radioresistant phenotype has been correlated with characteristics such as the enhanced repair of IR-induced DNA damage [1] [2] [3] [4], overexpression of cyclin D1 [5] [6], higher rates of cell growth and migration [7], a lower concentration of reactive oxygen species (ROS) in cells [8] [9] [10], inactivation of apoptotic proteins [11] and alterations in radiation-induced autophagy [12] [13]. A disadvantage of studying radioresistance is the lack of adequate radioresistant models reflecting the clinical features of this phenomenon.…”

“…The inherent variation among cells with different origins makes it difficult to determine the extent to which candidate factors contribute to cellular radioresistance and to identify factors that are essential for radioresistance. Isogenic models consisting of cells from the same origin that differ only in radioresistance have been increasingly pivotal in elucidating the cellular mechanisms of radioresistance [1] [7] [10] [14]. These models avoid the influence of confounding factors, allowing one to unravel the molecular mechanisms that are truly involved in radioresistance.…”

Simvastatin Enhances the Effects of Radiotherapy and Cetuximab on a Cell Line (FaDu) Derived from a Squamous Cell Carcinoma of Head and Neck

“…Simvastatin was dissolved in DMSO for cell culture experiments and used at doses ranging from 1 to 25 μM depending on the type of experiment, while it was dissolved in 1,2-propanediol in distilled water 1:1 (vol/vol) for animal treatments and used at a fixed dose of 50 mg/kg per day (simvastatin, DMSO, and propanediol were purchased from Sigma-Aldrich, St Louis, MO). Drug doses were based on preliminary studies from our group and previously published works [10] , [11] , [12] , [13] , [14] , [15] . We have varied doses and timings to adapt them to the type of assay to examine the effect of concomitancy between drugs for at least a period of 48 hours.…”