HDAC inhibitors reverse acquired radio resistance of KYSE-150R esophageal carcinoma cells by modulating Bmi-1 expression.
Tumors treated with fractionated doses of ionizing radiation (IR) often acquire radioresistance. Although histone deacetylase inhibitors (HDIs) have been demonstrated to sensitize intrinsic radioresistant cancer cell lines to IR, little is known on the impact of HDIs on the effects of IR in acquired radioresistant cancer cells. This study evaluates the mechanisms by which HDIs sensitize acquired radioresistant esophageal squamous cell carcinoma cells to IR. The HDIs trichostatin A and sodium butyrate were tested for the irability to sensitize acquired radioresistant KYSE-150R and radiosensitive KYSE-150 parental cells to IR. Although the HDIs induced similar levels of cytotoxicity in the KYSE-150 and the KYSE-150R cells, HDIs increased the: (i) radiosensitivity, (ii) IR-induced ROS generation, and (iii) IR-induced G2/M arrest and apoptosis of KYSE-150R cells compared with those of KYSE-150 cells. These changes were accompanied by increased p21 expression and decreased mitochondrial membrane potential. When combined with IR, HDIs inhibited Bmi-1 expression in KYSE-150R cells and their ability to repair DNA damage. The results demonstrate the potential utility of HDIs in augmenting the efficacy of fractionated radiotherapy.
Qinghua
Q
Dong
Sherven
S
Sharma
Hai
H
Liu
Long
L
Chen
Benxing
B
Gu
Xiaonan
X
Sun
Guanyu
G
Wang
D017209:Apoptosis / Q000528:radiation effects; D059447:Cell Cycle Checkpoints / Q000187:drug effects; D045744:Cell Line, Tumor; D053903:DNA Breaks, Double-Stranded / Q000187:drug effects; D004938:Esophageal Neoplasms / Q000473:pathology / Q000532:radiotherapy*; D056572:Histone Deacetylase Inhibitors / Q000494:pharmacology*; D006801:Humans; D008928:Mitochondria / Q000528:radiation effects; D063150:Polycomb Repressive Complex 1 / Q000235:genetics*; D011836:Radiation Tolerance / Q000187:drug effects*; D017382:Reactive Oxygen Species / Q000378:metabolism
C069077:BMI1 protein, human; D056572:Histone Deacetylase Inhibitors; D017382:Reactive Oxygen Species; D063150:Polycomb Repressive Complex 1