Identification of genes inducing resistance to ionizing radiation in human rectal cancer cell lines : re-sensitization of radio-resistant rectal cancer cells through down regulating NDRG1
Menée sur des lignées cellulaires de cancer humain du rectum, cette étude identifie des gènes induisant une résistance aux rayonnements ionisants, puis met en évidence une stratégie consistant à réduire le niveau d'expression du gène NDRG1 à l'aide d'un petit ARN en épingle à cheveux pour lever cette résistance
Background : Resistance to preoperative radiotherapy is a major clinical problem in the treatment for locally advanced rectal cancer. The role of NDRG1 in resistance to ionizing radiation in rectal cancer has not been fully elucidated. This study aimed to investigate the effect of the reduced intracellular NDRG1 expression on radio-sensitivity of human rectal cancer cells for exploring novel approaches for treatment of rectal cancer. Methods : Three radio-resistant human rectal cancer cell lines (SNU-61R80Gy, SNU-283R80Gy, and SNU-503R80Gy) were established from human rectal cancer cell lines (SNU-61, SNU-283, and SNU-503) using total 80 Gy of fractionated irradiation. Microarray analysis was performed to identify differently expressed genes in newly established radio-resistant human rectal cancer cells compared to parental rectal cancer cells. Results : A microarray analysis indicated the RNA expression of five genes (NDRG1, ERRFI1, H19, MPZL3, and UCA1) was highly increased in radio-resistant rectal cancer cell lines. Short hairpin RNA-mediated silencing of NDRG1 sensitized rectal cancer cell lines to clinically relevant doses of radiation by causing more DNA double strand breakages to rectal cancer cells when exposed to radiation. Conclusions : Targeting NDRG1 represents a promising strategy to increase response to radiotherapy in human rectal cancer.
BMC Cancer 2018