서울의대 / 김순찬, 신영경, 구자록*
Abstract
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.
Author information
Kim SC1,2, Shin YK1, Kim YA1, Jang SG1, Ku JL3,4.
1
Laboratory of Cell Biology, Cancer Research Institute, Seoul National University College of Medicine, 103 Daehak-ro, Jongno-gu, Seoul, 03080, Republic of Korea.
2
Department of Biomedical Sciences, Seoul National University College of Medicine, Seoul, 03080, Republic of Korea.
3
Laboratory of Cell Biology, Cancer Research Institute, Seoul National University College of Medicine, 103 Daehak-ro, Jongno-gu, Seoul, 03080, Republic of Korea. kujalok@snu.ac.kr.
4
Department of Biomedical Sciences, Seoul National University College of Medicine, Seoul, 03080, Republic of Korea. kujalok@snu.ac.kr.